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Insulin

Insulin (, from Latin insula, 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat, and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect, promoting widespread catabolism, especially of reserve body fat.

Beta cells are sensitive to blood sugar levels so that they secrete insulin into the blood in response to high level of glucose, and inhibit secretion of insulin when glucose levels are low. Insulin production is also regulated by glucose: high glucose promotes insulin production while low glucose levels lead to lower production. Insulin enhances glucose uptake and metabolism in the cells, thereby reducing blood sugar. Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon increases blood glucose by stimulating glycogenolysis and gluconeogenesis in the liver. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis.

Decreased or absent insulin activity results in diabetes, a condition of high blood sugar level (hyperglycaemia). There are two types of the disease. In type 1 diabetes, the beta cells are destroyed by an autoimmune reaction so that insulin can no longer be synthesized or be secreted into the blood. In type 2 diabetes, the destruction of beta cells is less pronounced than in type 1, and is not due to an autoimmune process. Instead, there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance are known to be involved. Type 2 diabetes is characterized by increased glucagon secretion which is unaffected by, and unresponsive to the concentration of blood glucose. But insulin is still secreted into the blood in response to the blood glucose. As a result, glucose accumulates in the blood.

The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a heterodimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin's structure varies slightly between species of animals. Insulin from non-human animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies.

Insulin was the first peptide hormone discovered. Frederick Banting and Charles Best, working in the laboratory of John Macleod at the University of Toronto, were the first to isolate insulin from dog pancreas in 1921. Frederick Sanger sequenced the amino acid structure in 1951, which made insulin the first protein to be fully sequenced. The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin in 1969. Insulin is also the first protein to be chemically synthesised and produced by DNA recombinant technology. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.

Evolution and species distribution
Insulin may have originated more than a billion years ago. The molecular origins of insulin go at least as far back as the simplest unicellular eukaryotes. Apart from animals, insulin-like proteins are also known to exist in fungi and protists.

Insulin is produced by beta cells of the pancreatic islets in most vertebrates and by the Brockmann body in some teleost fish. Cone snails: Conus geographus and Conus tulipa, venomous sea snails that hunt small fish, use modified forms of insulin in their venom cocktails. The insulin toxin, closer in structure to fishes' than to snails' native insulin, slows down the prey fishes by lowering their blood glucose levels.

Production
Insulin is produced exclusively in the beta cells of the pancreatic islets in mammals, and the Brockmann body in some fish. Human insulin is produced from the INS gene, located on chromosome 11. Rodents have two functional insulin genes; one is the homolog of most mammalian genes (Ins2), and the other is a retroposed copy that includes promoter sequence but that is missing an intron (Ins1). Transcription of the insulin gene increases in response to elevated blood glucose. This is primarily controlled by transcription factors that bind enhancer sequences in the ~400 base pairs before the gene's transcription start site.

The major transcription factors influencing insulin secretion are PDX1, NeuroD1, and MafA.

During a low-glucose state, PDX1 (pancreatic and duodenal homeobox protein 1) is located in the nuclear periphery as a result of interaction with HDAC1 and 2, which results in downregulation of insulin secretion. An increase in blood glucose levels causes phosphorylation of PDX1, which leads it to undergo nuclear translocation and bind the A3 element within the insulin promoter. Upon translocation it interacts with coactivators HAT p300 and SETD7. PDX1 affects the histone modifications through acetylation and deacetylation as well as methylation. It is also said to suppress glucagon.

NeuroD1, also known as β2, regulates insulin exocytosis in pancreatic β cells by directly inducing the expression of genes involved in exocytosis. It is localized in the cytosol, but in response to high glucose it becomes glycosylated by OGT and/or phosphorylated by ERK, which causes translocation to the nucleus. In the nucleus β2 heterodimerizes with E47, binds to the E1 element of the insulin promoter and recruits co-activator p300 which acetylates β2. It is able to interact with other transcription factors as well in activation of the insulin gene.

MafA is degraded by proteasomes upon low blood glucose levels. Increased levels of glucose make an unknown protein glycosylated. This protein works as a transcription factor for MafA in an unknown manner and MafA is transported out of the cell. MafA is then translocated back into the nucleus where it binds the C1 element of the insulin promoter.

These transcription factors work synergistically and in a complex arrangement. Increased blood glucose can after a while destroy the binding capacities of these proteins, and therefore reduce the amount of insulin secreted, causing diabetes. The decreased binding activities can be mediated by glucose induced oxidative stress and antioxidants are said to prevent the decreased insulin secretion in glucotoxic pancreatic β cells. Stress signalling molecules and reactive oxygen species inhibits the insulin gene by interfering with the cofactors binding the transcription factors and the transcription factors itself.

Several regulatory sequences in the promoter region of the human insulin gene bind to transcription factors. In general, the A-boxes bind to Pdx1 factors, E-boxes bind to NeuroD, C-boxes bind to MafA, and cAMP response elements to CREB. There are also silencers that inhibit transcription.

Synthesis

Insulin is synthesized as an inactive precursor molecule, a 110 amino acid-long protein called "preproinsulin". Preproinsulin is translated directly into the rough endoplasmic reticulum (RER), where its signal peptide is removed by signal peptidase to form "proinsulin". As the proinsulin folds, opposite ends of the protein, called the "A-chain" and the "B-chain", are fused together with three disulfide bonds. Folded proinsulin then transits through the Golgi apparatus and is packaged into specialized secretory vesicles. In the granule, proinsulin is cleaved by proprotein convertase 1/3 and proprotein convertase 2, removing the middle part of the protein, called the "C-peptide". Finally, carboxypeptidase E removes two pairs of amino acids from the protein's ends, resulting in active insulin – the insulin A- and B- chains, now connected with two disulfide bonds.

The resulting mature insulin is packaged inside mature granules waiting for metabolic signals (such as leucine, arginine, glucose and mannose) and vagal nerve stimulation to be exocytosed from the cell into the circulation.

Insulin and its related proteins have been shown to be produced inside the brain, and reduced levels of these proteins are linked to Alzheimer's disease.

Insulin release is stimulated also by beta-2 receptor stimulation and inhibited by alpha-1 receptor stimulation. In addition, cortisol, glucagon and growth hormone antagonize the actions of insulin during times of stress. Insulin also inhibits fatty acid release by hormone-sensitive lipase in adipose tissue.

Structure

Contrary to an initial belief that hormones would be generally small chemical molecules, as the first peptide hormone known of its structure, insulin was found to be quite large. A single protein (monomer) of human insulin is composed of 51 amino acids, and has a molecular mass of 5808 Da. The molecular formula of human insulin is C257H383N65O77S6. It is a combination of two peptide chains (dimer) named an A-chain and a B-chain, which are linked together by two disulfide bonds. The A-chain is composed of 21 amino acids, while the B-chain consists of 30 residues. The linking (interchain) disulfide bonds are formed at cysteine residues between the positions A7-B7 and A20-B19. There is an additional (intrachain) disulfide bond within the A-chain between cysteine residues at positions A6 and A11. The A-chain exhibits two α-helical regions at A1-A8 and A12-A19 which are antiparallel; while the B chain has a central α -helix (covering residues B9-B19) flanked by the disulfide bond on either sides and two β-sheets (covering B7-B10 and B20-B23).

The amino acid sequence of insulin is strongly conserved and varies only slightly between species. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one. Even insulin from some species of fish is similar enough to human to be clinically effective in humans. Insulin in some invertebrates is quite similar in sequence to human insulin, and has similar physiological effects. The strong homology seen in the insulin sequence of diverse species suggests that it has been conserved across much of animal evolutionary history. The C-peptide of proinsulin, however, differs much more among species; it is also a hormone, but a secondary one.

Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer. The hexamer is about 36000 Da in size. The six molecules are linked together as three dimeric units to form symmetrical molecule. An important feature is the presence of zinc atoms (Zn2+) on the axis of symmetry, which are surrounded by three water molecules and three histidine residues at position B10.

The hexamer is an inactive form with long-term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available. The hexamer-monomer conversion is one of the central aspects of insulin formulations for injection. The hexamer is far more stable than the monomer, which is desirable for practical reasons; however, the monomer is a much faster-reacting drug because diffusion rate is inversely related to particle size. A fast-reacting drug means insulin injections do not have to precede mealtimes by hours, which in turn gives people with diabetes more flexibility in their daily schedules. Insulin can aggregate and form fibrillar interdigitated beta-sheets. This can cause injection amyloidosis, and prevents the storage of insulin for long periods.

Secretion
Beta cells in the islets of Langerhans release insulin in two phases. The first-phase release is rapidly triggered in response to increased blood glucose levels, and lasts about 10 minutes. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours. The two phases of the insulin release suggest that insulin granules are present in diverse stated populations or "pools". During the first phase of insulin exocytosis, most of the granules predispose for exocytosis are released after the calcium internalization. This pool is known as Readily Releasable Pool (RRP). The RRP granules represent 0.3-0.7% of the total insulin-containing granule population, and they are found immediately adjacent to the plasma membrane. During the second phase of exocytosis, insulin granules require mobilization of granules to the plasma membrane and a previous preparation to undergo their release. Thus, the second phase of insulin release is governed by the rate at which granules get ready for release. This pool is known as a Reserve Pool (RP). The RP is released slower than the RRP (RRP: 18 granules/min; RP: 6 granules/min). Reduced first-phase insulin release may be the earliest detectable beta cell defect predicting onset of type 2 diabetes. First-phase release and insulin sensitivity are independent predictors of diabetes.

The description of first phase release is as follows:
 * Glucose enters the β-cells through the glucose transporters, GLUT 2. At low blood sugar levels little glucose enters the β-cells; at high blood glucose concentrations large quantities of glucose enter these cells.
 * The glucose that enters the β-cell is phosphorylated to glucose-6-phosphate (G-6-P) by glucokinase (hexokinase IV) which is not inhibited by G-6-P in the way that the hexokinases in other tissues (hexokinase I – III) are affected by this product. This means that the intracellular G-6-P concentration remains proportional to the blood sugar concentration.
 * Glucose-6-phosphate enters glycolytic pathway and then, via the pyruvate dehydrogenase reaction, into the Krebs cycle, where multiple, high-energy ATP molecules are produced by the oxidation of acetyl CoA (the Krebs cycle substrate), leading to a rise in the ATP:ADP ratio within the cell.
 * An increased intracellular ATP:ADP ratio closes the ATP-sensitive SUR1/Kir6.2 potassium channel (see sulfonylurea receptor). This prevents potassium ions (K+) from leaving the cell by facilitated diffusion, leading to a buildup of intracellular potassium ions. As a result, the inside of the cell becomes less negative with respect to the outside, leading to the depolarization of the cell surface membrane.
 * Upon depolarization, voltage-gated calcium ion (Ca2+) channels open, allowing calcium ions to move into the cell by facilitated diffusion.
 * The cytosolic calcium ion concentration can also be increased by calcium release from intracellular stores via activation of ryanodine receptors.
 * The calcium ion concentration in the cytosol of the beta cells can also, or additionally, be increased through the activation of phospholipase C resulting from the binding of an extracellular ligand (hormone or neurotransmitter) to a G protein-coupled membrane receptor. Phospholipase C cleaves the membrane phospholipid, phosphatidyl inositol 4,5-bisphosphate, into inositol 1,4,5-trisphosphate and diacylglycerol. Inositol 1,4,5-trisphosphate (IP3) then binds to receptor proteins in the plasma membrane of the endoplasmic reticulum (ER). This allows the release of Ca2+ ions from the ER via IP3-gated channels, which raises the cytosolic concentration of calcium ions independently of the effects of a high blood glucose concentration. Parasympathetic stimulation of the pancreatic islets operates via this pathway to increase insulin secretion into the blood.
 * The significantly increased amount of calcium ions in the cells' cytoplasm causes the release into the blood of previously synthesized insulin, which has been stored in intracellular secretory vesicles.

This is the primary mechanism for release of insulin. Other substances known to stimulate insulin release include the amino acids arginine and leucine, parasympathetic release of acetylcholine (acting via the phospholipase C pathway), sulfonylurea, cholecystokinin (CCK, also via phospholipase C), and the gastrointestinally derived incretins, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP).

Release of insulin is strongly inhibited by norepinephrine (noradrenaline), which leads to increased blood glucose levels during stress. It appears that release of catecholamines by the sympathetic nervous system has conflicting influences on insulin release by beta cells, because insulin release is inhibited by α2-adrenergic receptors and stimulated by β2-adrenergic receptors. The net effect of norepinephrine from sympathetic nerves and epinephrine from adrenal glands on insulin release is inhibition due to dominance of the α-adrenergic receptors.

When the glucose level comes down to the usual physiologic value, insulin release from the β-cells slows or stops. If the blood glucose level drops lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from islet of Langerhans alpha cells) forces release of glucose into the blood from the liver glycogen stores, supplemented by gluconeogenesis if the glycogen stores become depleted. By increasing blood glucose, the hyperglycemic hormones prevent or correct life-threatening hypoglycemia.

Evidence of impaired first-phase insulin release can be seen in the glucose tolerance test, demonstrated by a substantially elevated blood glucose level at 30 minutes after the ingestion of a glucose load (75 or 100 g of glucose), followed by a slow drop over the next 100 minutes, to remain above 120 mg/100 mL after two hours after the start of the test. In a normal person the blood glucose level is corrected (and may even be slightly over-corrected) by the end of the test. An insulin spike is a 'first response' to blood glucose increase, this response is individual and dose specific although it was always previously assumed to be food type specific only.

Oscillations

Even during digestion, in general, one or two hours following a meal, insulin release from the pancreas is not continuous, but oscillates with a period of 3–6 minutes, changing from generating a blood insulin concentration more than about 800 p mol/l to less than 100 pmol/L (in rats). This is thought to avoid downregulation of insulin receptors in target cells, and to assist the liver in extracting insulin from the blood. This oscillation is important to consider when administering insulin-stimulating medication, since it is the oscillating blood concentration of insulin release, which should, ideally, be achieved, not a constant high concentration. This may be achieved by delivering insulin rhythmically to the portal vein, by light activated delivery, or by islet cell transplantation to the liver.

Blood insulin level
The blood insulin level can be measured in international units, such as μIU/mL or in molar concentration, such as pmol/L, where 1 μIU/mL equals 6.945 pmol/L. A typical blood level between meals is 8–11 μIU/mL (57–79 pmol/L).

Signal transduction
The effects of insulin are initiated by its binding to a receptor, the insulin receptor (IR), present in the cell membrane. The receptor molecule contains an α- and β subunits. Two molecules are joined to form what is known as a homodimer. Insulin binds to the α-subunits of the homodimer, which faces the extracellular side of the cells. The β subunits have tyrosine kinase enzyme activity which is triggered by the insulin binding. This activity provokes the autophosphorylation of the β subunits and subsequently the phosphorylation of proteins inside the cell known as insulin receptor substrates (IRS). The phosphorylation of the IRS activates a signal transduction cascade that leads to the activation of other kinases as well as transcription factors that mediate the intracellular effects of insulin.

The cascade that leads to the insertion of GLUT4 glucose transporters into the cell membranes of muscle and fat cells, and to the synthesis of glycogen in liver and muscle tissue, as well as the conversion of glucose into triglycerides in liver, adipose, and lactating mammary gland tissue, operates via the activation, by IRS-1, of phosphoinositol 3 kinase (PI3K). This enzyme converts a phospholipid in the cell membrane by the name of phosphatidylinositol 4,5-bisphosphate (PIP2), into phosphatidylinositol 3,4,5-triphosphate (PIP3), which, in turn, activates protein kinase B (PKB). Activated PKB facilitates the fusion of GLUT4 containing endosomes with the cell membrane, resulting in an increase in GLUT4 transporters in the plasma membrane. PKB also phosphorylates glycogen synthase kinase (GSK), thereby inactivating this enzyme. This means that its substrate, glycogen synthase (GS), cannot be phosphorylated, and remains dephosphorylated, and therefore active. The active enzyme, glycogen synthase (GS), catalyzes the rate limiting step in the synthesis of glycogen from glucose. Similar dephosphorylations affect the enzymes controlling the rate of glycolysis leading to the synthesis of fats via malonyl-CoA in the tissues that can generate triglycerides, and also the enzymes that control the rate of gluconeogenesis in the liver. The overall effect of these final enzyme dephosphorylations is that, in the tissues that can carry out these reactions, glycogen and fat synthesis from glucose are stimulated, and glucose production by the liver through glycogenolysis and gluconeogenesis are inhibited. The breakdown of triglycerides by adipose tissue into free fatty acids and glycerol is also inhibited.

After the intracellular signal that resulted from the binding of insulin to its receptor has been produced, termination of signaling is then needed. As mentioned below in the section on degradation, endocytosis and degradation of the receptor bound to insulin is a main mechanism to end signaling. In addition, the signaling pathway is also terminated by dephosphorylation of the tyrosine residues in the various signaling pathways by tyrosine phosphatases. Serine/Threonine kinases are also known to reduce the activity of insulin.

The structure of the insulin–insulin receptor complex has been determined using the techniques of X-ray crystallography.

Physiological effects

The actions of insulin on the global human metabolism level include:
 * Increase of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about two-thirds of body cells)
 * Increase of DNA replication and protein synthesis via control of amino acid uptake
 * Modification of the activity of numerous enzymes.

The actions of insulin (indirect and direct) on cells include:
 * Stimulates the uptake of glucose – Insulin decreases blood glucose concentration by inducing intake of glucose by the cells. This is possible because Insulin causes the insertion of the GLUT4 transporter in the cell membranes of muscle and fat tissues which allows glucose to enter the cell.
 * Increased fat synthesis – insulin forces fat cells to take in blood glucose, which is converted into triglycerides; decrease of insulin causes the reverse.
 * Increased esterification of fatty acids – forces adipose tissue to make neutral fats (i.e., triglycerides) from fatty acids; decrease of insulin causes the reverse.
 * Decreased lipolysis in – forces reduction in conversion of fat cell lipid stores into blood fatty acids and glycerol; decrease of insulin causes the reverse.
 * Induced glycogen synthesis – When glucose levels are high, insulin induces the formation of glycogen by the activation of the hexokinase enzyme, which adds a phosphate group in glucose, thus resulting in a molecule that cannot exit the cell. At the same time, insulin inhibits the enzyme glucose-6-phosphatase, which removes the phosphate group. These two enzymes are key for the formation of glycogen. Also, insulin activates the enzymes phosphofructokinase and glycogen synthase which are responsible for glycogen synthesis.
 * Decreased gluconeogenesis and glycogenolysis – decreases production of glucose from noncarbohydrate substrates, primarily in the liver (the vast majority of endogenous insulin arriving at the liver never leaves the liver); decrease of insulin causes glucose production by the liver from assorted substrates.
 * Decreased proteolysis – decreasing the breakdown of protein
 * Decreased autophagy – decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely.
 * Increased amino acid uptake – forces cells to absorb circulating amino acids; decrease of insulin inhibits absorption.
 * Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in microarteries; decrease of insulin reduces flow by allowing these muscles to contract.
 * Increase in the secretion of hydrochloric acid by parietal cells in the stomach.
 * Increased potassium uptake – forces cells synthesizing glycogen (a very spongy, "wet" substance, that increases the content of intracellular water, and its accompanying K+ ions) to absorb potassium from the extracellular fluids; lack of insulin inhibits absorption. Insulin's increase in cellular potassium uptake lowers potassium levels in blood plasma. This possibly occurs via insulin-induced translocation of the Na+/K+-ATPase to the surface of skeletal muscle cells.
 * Decreased renal sodium excretion.
 * In hepatocytes, insulin binding acutely leads to activation of protein phosphatase 2A (PP2A), which dephosphorylates the bifunctional enzyme fructose bisphosphatase-2 (PFKB1), activating the phosphofructokinase-2 (PFK-2) active site. PFK-2 increases production of fructose 2,6-bisphosphate. Fructose 2,6-bisphosphate allosterically activates PFK-1, which favors glycolysis over gluconeogenesis. Increased glycolysis increases the formation of malonyl-CoA, a molecule that can be shunted into lipogenesis and that allosterically inhibits of  carnitine palmitoyltransferase I (CPT1), a mitochondrial enzyme necessary for the translocation of fatty acids into the intermembrane space of the mitochondria for fatty acid metabolism.

Insulin also influences other body functions, such as vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular. Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the co-ordination of a wide variety of homeostatic or regulatory processes in the human body. Insulin also has stimulatory effects on gonadotropin-releasing hormone from the hypothalamus, thus favoring fertility.

Degradation
Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment, or it may be degraded by the cell. The two primary sites for insulin clearance are the liver and the kidney. It is broken down by the enzyme, protein-disulfide reductase (glutathione), which breaks the disulphide bonds between the A and B chains. The liver clears most insulin during first-pass transit, whereas the kidney clears most of the insulin in systemic circulation. Degradation normally involves endocytosis of the insulin-receptor complex, followed by the action of insulin-degrading enzyme. An insulin molecule produced endogenously by the beta cells is estimated to be degraded within about one hour after its initial release into circulation (insulin half-life ~ 4–6 minutes).

Regulator of endocannabinoid metabolism
Insulin is a major regulator of endocannabinoid (EC) metabolism and insulin treatment has been shown to reduce intracellular ECs, the 2-arachidonoylglycerol (2-AG) and anandamide (AEA), which correspond with insulin-sensitive expression changes in enzymes of EC metabolism. In insulin-resistant adipocytes, patterns of insulin-induced enzyme expression is disturbed in a manner consistent with elevated EC synthesis and reduced EC degradation. Findings suggest that insulin-resistant adipocytes fail to regulate EC metabolism and decrease intracellular EC levels in response to insulin stimulation, whereby obese insulin-resistant individuals exhibit increased concentrations of ECs. This dysregulation contributes to excessive visceral fat accumulation and reduced adiponectin release from abdominal adipose tissue, and further to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes.

Hypoglycemia
Hypoglycemia, also known as "low blood sugar", is when blood sugar decreases to below normal levels. This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures or death. A feeling of hunger, sweating, shakiness and weakness may also be present. Symptoms typically come on quickly.

The most common cause of hypoglycemia is medications used to treat diabetes such as insulin and sulfonylureas. Risk is greater in diabetics who have eaten less than usual, exercised more than usual or have consumed alcohol. Other causes of hypoglycemia include kidney failure, certain tumors, such as insulinoma, liver disease, hypothyroidism, starvation, inborn error of metabolism, severe infections, reactive hypoglycemia and a number of drugs including alcohol. Low blood sugar may occur in otherwise healthy babies who have not eaten for a few hours.

Diseases and syndromes
There are several conditions in which insulin disturbance is pathologic:
 * Diabetes – general term referring to all states characterized by hyperglycemia. It can be of the following types:
 * Type 1 diabetes – autoimmune-mediated destruction of insulin-producing β-cells in the pancreas, resulting in absolute insulin deficiency
 * Type 2 diabetes – either inadequate insulin production by the β-cells or insulin resistance or both because of reasons not completely understood.
 * there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys; importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors, though this may not be a causal relationship.
 * it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions
 * Other types of impaired glucose tolerance (see Diabetes)
 * Insulinoma – a tumor of beta cells producing excess insulin or reactive hypoglycemia.
 * Metabolic syndrome – a poorly understood condition first called syndrome X by Gerald Reaven. It is not clear whether the syndrome has a single, treatable cause, or is the result of body changes leading to type 2 diabetes. It is characterized by elevated blood pressure, dyslipidemia (disturbances in blood cholesterol forms and other blood lipids), and increased waist circumference (at least in populations in much of the developed world). The basic underlying cause may be the insulin resistance that precedes type 2 diabetes, which is a diminished capacity for insulin response in some tissues (e.g., muscle, fat). It is common for morbidities such as essential hypertension, obesity, type 2 diabetes, and cardiovascular disease (CVD) to develop.
 * Polycystic ovary syndrome – a complex syndrome in women in the reproductive years where anovulation and androgen excess are commonly displayed as hirsutism. In many cases of PCOS, insulin resistance is present.

Medical uses
Biosynthetic human insulin (insulin human rDNA, INN) for clinical use is manufactured by recombinant DNA technology. Biosynthetic human insulin has increased purity when compared with extractive animal insulin, enhanced purity reducing antibody formation. Researchers have succeeded in introducing the gene for human insulin into plants as another method of producing insulin ("biopharming") in safflower. This technique is anticipated to reduce production costs.

Several analogs of human insulin are available. These insulin analogs are closely related to the human insulin structure, and were developed for specific aspects of glycemic control in terms of fast action (prandial insulins) and long action (basal insulins). The first biosynthetic insulin analog was developed for clinical use at mealtime (prandial insulin), Humalog (insulin lispro), it is more rapidly absorbed after subcutaneous injection than regular insulin, with an effect 15 minutes after injection. Other rapid-acting analogues are NovoRapid and Apidra, with similar profiles. All are rapidly absorbed due to amino acid sequences that will reduce formation of dimers and hexamers (monomeric insulins are more rapidly absorbed). Fast acting insulins do not require the injection-to-meal interval previously recommended for human insulin and animal insulins. The other type is long acting insulin; the first of these was Lantus (insulin glargine). These have a steady effect for an extended period from 18 to 24 hours. Likewise, another protracted insulin analogue (Levemir) is based on a fatty acid acylation approach. A myristic acid molecule is attached to this analogue, which associates the insulin molecule to the abundant serum albumin, which in turn extends the effect and reduces the risk of hypoglycemia. Both protracted analogues need to be taken only once daily, and are used for type 1 diabetics as the basal insulin. A combination of a rapid acting and a protracted insulin is also available, making it more likely for patients to achieve an insulin profile that mimics that of the body's own insulin release. Insulin is also used in many cell lines, such as CHO-s, HEK 293 or Sf9, for the manufacturing of monoclonal antibodies, virus vaccines, and gene therapy products.

Insulin is usually taken as subcutaneous injections by single-use syringes with needles, via an insulin pump, or by repeated-use insulin pens with disposable needles. Inhaled insulin is also available in the U.S. market.

The Dispovan Single-Use Pen Needle by HMD is India’s first insulin pen needle that makes self-administration easy. Featuring extra-thin walls and a multi-bevel tapered point, these pen needles prioritise patient comfort by minimising pain and ensuring seamless medication delivery. The product aims to provide affordable Pen Needles to the developing part of the country through its wide distribution channel. Additionally, the universal design of these needles guarantees compatibility with all insulin pens.

Unlike many medicines, insulin cannot be taken by mouth because, like nearly all other proteins introduced into the gastrointestinal tract, it is reduced to fragments, whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered orally or sublingually.

In 2021, the World Health Organization added insulin to its model list of essential medicines.

Insulin, and all other medications, are supplied free of charge to people with diabetes by the National Health Service in the countries of the United Kingdom.

Discovery
In 1869, while studying the structure of the pancreas under a microscope, Paul Langerhans, a medical student in Berlin, identified some previously unnoticed tissue clumps scattered throughout the bulk of the pancreas. The function of the "little heaps of cells", later known as the islets of Langerhans, initially remained unknown, but Édouard Laguesse later suggested they might produce secretions that play a regulatory role in digestion. Paul Langerhans' son, Archibald, also helped to understand this regulatory role.

In 1889, the physician Oskar Minkowski, in collaboration with Joseph von Mering, removed the pancreas from a healthy dog to test its assumed role in digestion. On testing the urine, they found sugar, establishing for the first time a relationship between the pancreas and diabetes. In 1901, another major step was taken by the American physician and scientist Eugene Lindsay Opie, when he isolated the role of the pancreas to the islets of Langerhans: "Diabetes mellitus when the result of a lesion of the pancreas is caused by destruction of the islands of Langerhans and occurs only when these bodies are in part or wholly destroyed".

Over the next two decades researchers made several attempts to isolate the islets' secretions. In 1906 George Ludwig Zuelzer achieved partial success in treating dogs with pancreatic extract, but he was unable to continue his work. Between 1911 and 1912, E.L. Scott at the University of Chicago tried aqueous pancreatic extracts and noted "a slight diminution of glycosuria", but was unable to convince his director of his work's value; it was shut down. Israel Kleiner demonstrated similar effects at Rockefeller University in 1915, but World War I interrupted his work and he did not return to it.

In 1916, Nicolae Paulescu developed an aqueous pancreatic extract which, when injected into a diabetic dog, had a normalizing effect on blood sugar levels. He had to interrupt his experiments because of World War I, and in 1921 he wrote four papers about his work carried out in Bucharest and his tests on a diabetic dog. Later that year, he published "Research on the Role of the Pancreas in Food Assimilation".

The name "insulin" was coined by Edward Albert Sharpey-Schafer in 1916 for a hypothetical molecule produced by pancreatic islets of Langerhans (Latin insula for islet or island) that controls glucose metabolism. Unbeknown to Sharpey-Schafer, Jean de Meyer had introduced the very similar word "insuline" in 1909 for the same molecule.

Extraction and purification
In October 1920, Canadian Frederick Banting concluded that the digestive secretions that Minkowski had originally studied were breaking down the islet secretion, thereby making it impossible to extract successfully. A surgeon by training, Banting knew that blockages of the pancreatic duct would lead most of the pancreas to atrophy, while leaving the islets of Langerhans intact. He reasoned that a relatively pure extract could be made from the islets once most of the rest of the pancreas was gone. He jotted a note to himself: "Ligate pancreatic ducts of dog. Keep dogs alive till acini degenerate leaving Islets. Try to isolate the internal secretion of these + relieve glycosurea[sic]." In the spring of 1921, Banting traveled to Toronto to explain his idea to John Macleod, Professor of Physiology at the University of Toronto. Macleod was initially skeptical, since Banting had no background in research and was not familiar with the latest literature, but he agreed to provide lab space for Banting to test out his ideas. Macleod also arranged for two undergraduates to be Banting's lab assistants that summer, but Banting required only one lab assistant. Charles Best and Clark Noble flipped a coin; Best won the coin toss and took the first shift. This proved unfortunate for Noble, as Banting kept Best for the entire summer and eventually shared half his Nobel Prize money and credit for the discovery with Best. On 30 July 1921, Banting and Best successfully isolated an extract ("isletin") from the islets of a duct-tied dog and injected it into a diabetic dog, finding that the extract reduced its blood sugar by 40% in 1 hour.

Banting and Best presented their results to Macleod on his return to Toronto in the fall of 1921, but Macleod pointed out flaws with the experimental design, and suggested the experiments be repeated with more dogs and better equipment. He moved Banting and Best into a better laboratory and began paying Banting a salary from his research grants. Several weeks later, the second round of experiments was also a success, and Macleod helped publish their results privately in Toronto that November. Bottlenecked by the time-consuming task of duct-tying dogs and waiting several weeks to extract insulin, Banting hit upon the idea of extracting insulin from the fetal calf pancreas, which had not yet developed digestive glands. By December, they had also succeeded in extracting insulin from the adult cow pancreas. Macleod discontinued all other research in his laboratory to concentrate on the purification of insulin. He invited biochemist James Collip to help with this task, and the team felt ready for a clinical test within a month. On 11 January 1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin. However, the extract was so impure that Thompson had a severe allergic reaction, and further injections were cancelled. Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract. A second dose was injected on 23 January, eliminating the glycosuria that was typical of diabetes without causing any obvious side-effects. The first American patient was Elizabeth Hughes, the daughter of U.S. Secretary of State Charles Evans Hughes. The first patient treated in the U.S. was future woodcut artist James D. Havens; John Ralston Williams imported insulin from Toronto to Rochester, New York, to treat Havens.

Banting and Best never worked well with Collip, regarding him as something of an interloper, and Collip left the project soon after. Over the spring of 1922, Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure. The drug firm Eli Lilly and Company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April. In November, Lilly's head chemist, George B. Walden discovered isoelectric precipitation and was able to produce large quantities of highly refined insulin. Shortly thereafter, insulin was offered for sale to the general public.

Patent
Toward the end of January 1922, tensions mounted between the four "co-discoverers" of insulin and Collip briefly threatened to separately patent his purification process. John G. FitzGerald, director of the non-commercial public health institution Connaught Laboratories, therefore stepped in as peacemaker. The resulting agreement of 25 January 1922 established two key conditions: 1) that the collaborators would sign a contract agreeing not to take out a patent with a commercial pharmaceutical firm during an initial working period with Connaught; and 2) that no changes in research policy would be allowed unless first discussed among FitzGerald and the four collaborators. It helped contain disagreement and tied the research to Connaught's public mandate.

Initially, Macleod and Banting were particularly reluctant to patent their process for insulin on grounds of medical ethics. However, concerns remained that a private third-party would hijack and monopolize the research (as Eli Lilly and Company had hinted ), and that safe distribution would be difficult to guarantee without capacity for quality control. To this end, Edward Calvin Kendall gave valuable advice. He had isolated thyroxin at the Mayo Clinic in 1914 and patented the process through an arrangement between himself, the brothers Mayo, and the University of Minnesota, transferring the patent to the public university. On 12 April, Banting, Best, Collip, Macleod, and FitzGerald wrote jointly to the president of the University of Toronto to propose a similar arrangement with the aim of assigning a patent to the Board of Governors of the university. The letter emphasized that: "The patent would not be used for any other purpose than to prevent the taking out of a patent by other persons. When the details of the method of preparation are published anyone would be free to prepare the extract, but no one could secure a profitable monopoly."The assignment to the University of Toronto Board of Governors was completed on 15 January 1923, for the token payment of $1.00. The arrangement was congratulated in The World's Work in 1923 as "a step forward in medical ethics". It has also received much media attention in the 2010s regarding the issue of healthcare and drug affordability.

Following further concern regarding Eli Lilly's attempts to separately patent parts of the manufacturing process, Connaught's Assistant Director and Head of the Insulin Division Robert Defries established a patent pooling policy which would require producers to freely share any improvements to the manufacturing process without compromising affordability.

Structural analysis and synthesis
Purified animal-sourced insulin was initially the only type of insulin available for experiments and diabetics. John Jacob Abel was the first to produce the crystallised form in 1926. Evidence of the protein nature was first given by Michael Somogyi, Edward A. Doisy, and Philip A. Shaffer in 1924. It was fully proven when Hans Jensen and Earl A. Evans Jr. isolated the amino acids phenylalanine and proline in 1935.

The amino acid structure of insulin was first characterized in 1951 by Frederick Sanger, and the first synthetic insulin was produced simultaneously in the labs of Panayotis Katsoyannis at the University of Pittsburgh and Helmut Zahn at RWTH Aachen University in the mid-1960s. Synthetic crystalline bovine insulin was achieved by Chinese researchers in 1965. The complete 3-dimensional structure of insulin was determined by X-ray crystallography in Dorothy Hodgkin's laboratory in 1969.

Hans E. Weber discovered preproinsulin while working as a research fellow at the University of California Los Angeles in 1974. In 1973–1974, Weber learned the techniques of how to isolate, purify, and translate messenger RNA. To further investigate insulin, he obtained pancreatic tissues from a slaughterhouse in Los Angeles and then later from animal stock at UCLA. He isolated and purified total messenger RNA from pancreatic islet cells which was then translated in oocytes from Xenopus laevis and precipitated using anti-insulin antibodies. When total translated protein was run on an SDS-polyacrylamide gel electrophoresis and sucrose gradient, peaks corresponding to insulin and proinsulin were isolated. However, to the surprise of Weber a third peak was isolated corresponding to a molecule larger than proinsulin. After reproducing the experiment several times, he consistently noted this large peak prior to proinsulin that he determined must be a larger precursor molecule upstream of proinsulin. In May 1975, at the American Diabetes Association meeting in New York, Weber gave an oral presentation of his work where he was the first to name this precursor molecule "preproinsulin". Following this oral presentation, Weber was invited to dinner to discuss his paper and findings by Donald Steiner, a researcher who contributed to the characterization of proinsulin. A year later in April 1976, this molecule was further characterized and sequenced by Steiner, referencing the work and discovery of Hans Weber. Preproinsulin became an important molecule to study the process of transcription and translation.

The first genetically engineered, synthetic "human" insulin was produced using E. coli in 1978 by Arthur Riggs and Keiichi Itakura at the Beckman Research Institute of the City of Hope in collaboration with Herbert Boyer at Genentech. Genentech, founded by Swanson, Boyer and Eli Lilly and Company, went on in 1982 to sell the first commercially available biosynthetic human insulin under the brand name Humulin. The vast majority of insulin used worldwide is biosynthetic recombinant "human" insulin or its analogues. Recently, another approach has been used by a pioneering group of Canadian researchers, using an easily grown safflower plant, for the production of much cheaper insulin.

Recombinant insulin is produced either in yeast (usually Saccharomyces cerevisiae) or E. coli. In yeast, insulin may be engineered as a single-chain protein with a KexII endoprotease (a yeast homolog of PCI/PCII) site that separates the insulin A chain from a C-terminally truncated insulin B chain. A chemically synthesized C-terminal tail is then grafted onto insulin by reverse proteolysis using the inexpensive protease trypsin; typically the lysine on the C-terminal tail is protected with a chemical protecting group to prevent proteolysis. The ease of modular synthesis and the relative safety of modifications in that region accounts for common insulin analogs with C-terminal modifications (e.g. lispro, aspart, glulisine). The Genentech synthesis and completely chemical synthesis such as that by Bruce Merrifield are not preferred because the efficiency of recombining the two insulin chains is low, primarily due to competition with the precipitation of insulin B chain.

Nobel Prizes

The Nobel Prize committee in 1923 credited the practical extraction of insulin to a team at the University of Toronto and awarded the Nobel Prize to two men: Frederick Banting and John Macleod. They were awarded the Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin. Banting, incensed that Best was not mentioned, shared his prize with him, and Macleod immediately shared his with James Collip. The patent for insulin was sold to the University of Toronto for one dollar.

Two other Nobel Prizes have been awarded for work on insulin. British molecular biologist Frederick Sanger, who determined the primary structure of insulin in 1955, was awarded the 1958 Nobel Prize in Chemistry. Rosalyn Sussman Yalow received the 1977 Nobel Prize in Medicine for the development of the radioimmunoassay for insulin.

Several Nobel Prizes also have an indirect connection with insulin. George Minot, co-recipient of the 1934 Nobel Prize for the development of the first effective treatment for pernicious anemia, had diabetes. William Castle observed that the 1921 discovery of insulin, arriving in time to keep Minot alive, was therefore also responsible for the discovery of a cure for pernicious anemia. Dorothy Hodgkin was awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography, the technique she used for deciphering the complete molecular structure of insulin in 1969.

Controversy

The work published by Banting, Best, Collip and Macleod represented the preparation of purified insulin extract suitable for use on human patients. Although Paulescu discovered the principles of the treatment, his saline extract could not be used on humans; he was not mentioned in the 1923 Nobel Prize. Ian Murray was particularly active in working to correct "the historical wrong" against Nicolae Paulescu. Murray was a professor of physiology at the Anderson College of Medicine in Glasgow, Scotland, the head of the department of Metabolic Diseases at a leading Glasgow hospital, vice-president of the British Association of Diabetes, and a founding member of the International Diabetes Federation. Murray wrote:

"Insufficient recognition has been given to Paulescu, the distinguished Romanian scientist, who at the time when the Toronto team were commencing their research had already succeeded in extracting the antidiabetic hormone of the pancreas and proving its efficacy in reducing the hyperglycaemia in diabetic dogs."

In a private communication, Arne Tiselius, former head of the Nobel Institute, expressed his personal opinion that Paulescu was equally worthy of the award in 1923.

title: Insulin


text:
Inductor

An inductor, also called a coil, choke, or reactor, is a passive two-terminal electrical component that stores energy in a magnetic field when electric current flows through it. An inductor typically consists of an insulated wire wound into a coil.

When the current flowing through the coil changes, the time-varying magnetic field induces an electromotive force (emf) (voltage) in the conductor, described by Faraday's law of induction. According to Lenz's law, the induced voltage has a polarity (direction) which opposes the change in current that created it. As a result, inductors oppose any changes in current through them.

An inductor is characterized by its inductance, which is the ratio of the voltage to the rate of change of current. In the International System of Units (SI), the unit of inductance is the henry (H) named for 19th century American scientist Joseph Henry. In the measurement of magnetic circuits, it is equivalent to $weber⁄ampere$. Inductors have values that typically range from 1μH (10−6H) to 20H. Many inductors have a magnetic core made of iron or ferrite inside the coil, which serves to increase the magnetic field and thus the inductance. Along with capacitors and resistors, inductors are one of the three passive linear circuit elements that make up electronic circuits. Inductors are widely used in alternating current (AC) electronic equipment, particularly in radio equipment. They are used to block AC while allowing DC to pass; inductors designed for this purpose are called chokes. They are also used in electronic filters to separate signals of different frequencies, and in combination with capacitors to make tuned circuits, used to tune radio and TV receivers.

The term inductor seems to come from Heinrich Daniel Ruhmkorff, who called the induction coil he invented in 1851 an inductorium.

Description

An electric current flowing through a conductor generates a magnetic field surrounding it. The magnetic flux linkage $$\Phi_\mathbf{B}$$ generated by a given current $$I$$ depends on the geometric shape of the circuit. Their ratio defines the inductance $$L$$. Thus
 * $$L := \frac{\Phi_\mathbf{B}}{I}$$.

The inductance of a circuit depends on the geometry of the current path as well as the magnetic permeability of nearby materials. An inductor is a component consisting of a wire or other conductor shaped to increase the magnetic flux through the circuit, usually in the shape of a coil or helix, with two terminals. Winding the wire into a coil increases the number of times the magnetic flux lines link the circuit, increasing the field and thus the inductance. The more turns, the higher the inductance. The inductance also depends on the shape of the coil, separation of the turns, and many other factors. By adding a "magnetic core" made of a ferromagnetic material like iron inside the coil, the magnetizing field from the coil will induce magnetization in the material, increasing the magnetic flux. The high permeability of a ferromagnetic core can increase the inductance of a coil by a factor of several thousand over what it would be without it.

Constitutive equation
Any change in the current through an inductor creates a changing flux, inducing a voltage across the inductor. By Faraday's law of induction, the voltage $$\mathcal{E}$$ induced by any change in magnetic flux through the circuit is given by
 * $$\mathcal{E} = -\frac{d\Phi_\mathbf{B}}{dt}$$.

Reformulating the definition of $L$ above, we obtain
 * $$ \Phi_\mathbf{B} = LI$$.

It follows that
 * $$\mathcal{E} = -\frac{d\Phi_\mathbf{B}}{dt} = -\frac{d}{dt}(LI)$$

$$ if $L$ is independent of time, current and magnetic flux linkage. Thus, inductance is also a measure of the amount of electromotive force (voltage) generated for a given rate of change of current. This is usually taken to be the constitutive relation (defining equation) of the inductor.

Lenz's law
The polarity (direction) of the induced voltage is given by Lenz's law, which states that the induced voltage will be such as to oppose the change in current. For example, if the current through a 1 henry inductor is increasing at a rate of 1 amperes per second, the induced 1 volt of potential difference will be positive at the current's entrance point and negative at the exit point, tending to oppose the additional current. The energy from the external circuit necessary to overcome this potential "hill" is being stored in the magnetic field of the inductor. If the current is decreasing, the induced voltage will be negative at the current's entrance point and positive at the exit point, tending to maintain the current. In this case energy from the magnetic field is being returned to the circuit.

Positive form of current–voltage relationship
Because the induced voltage is positive at the current's entrance terminal, the inductor's current–voltage relationship is often expressed without a negative sign by using the current's exit terminal as the reference point for the voltage $$V(t)$$ at the current's entrance terminal (as labeled in the schematic).

The derivative form of this current–voltage relationship is then:$$V(t) = L\frac{\mathrm{d}I(t)}{\mathrm{d}t} \, .$$The integral form of this current–voltage relationship, starting at time $$t_0$$ with some initial current $$I(t_0)$$, is then:$$I(t) = I(t_0) + \frac{1}{L}\int_{t_0}^t V(\tau) \, \mathrm{d}\tau \, .$$The dual of the inductor is the capacitor, which stores energy in an electric field rather than a magnetic field. Its current–voltage relation replaces $L$ with the capacitance $C$ and has current and voltage swapped from these equations.

Energy stored in an inductor
One intuitive explanation as to why a potential difference is induced on a change of current in an inductor goes as follows:

When there is a change in current through an inductor there is a change in the strength of the magnetic field. For example, if the current is increased, the magnetic field increases. This, however, does not come without a price. The magnetic field contains potential energy, and increasing the field strength requires more energy to be stored in the field. This energy comes from the electric current through the inductor. The increase in the magnetic potential energy of the field is provided by a corresponding drop in the electric potential energy of the charges flowing through the windings. This appears as a voltage drop across the windings as long as the current increases. Once the current is no longer increased and is held constant, the energy in the magnetic field is constant and no additional energy must be supplied, so the voltage drop across the windings disappears.

Similarly, if the current through the inductor decreases, the magnetic field strength decreases, and the energy in the magnetic field decreases. This energy is returned to the circuit in the form of an increase in the electrical potential energy of the moving charges, causing a voltage rise across the windings.

Derivation
The work done per unit charge on the charges passing through the inductor is $$-\mathcal{E}$$. The negative sign indicates that the work is done against the emf, and is not done by the emf. The current $$I$$ is the charge per unit time passing through the inductor. Therefore, the rate of work $$W$$ done by the charges against the emf, that is the rate of change of energy of the current, is given by
 * $$\frac{dW}{dt} = -\mathcal{E}I $$

From the constitutive equation for the inductor, $$-\mathcal{E} = L\frac{dI}{dt}$$ so
 * $$\frac{dW}{dt}= L\frac{dI}{dt} \cdot I = LI \cdot \frac{dI}{dt}$$

 * $$dW = L I \cdot dI$$

In a ferromagnetic core inductor, when the magnetic field approaches the level at which the core saturates, the inductance will begin to change, it will be a function of the current $$L(I)$$. Neglecting losses, the energy $$W$$ stored by an inductor with a current $$I_0$$ passing through it is equal to the amount of work required to establish the current through the inductor.

This is given by: $$W = \int_0^{I_0} L_d(I) \, I \, dI$$, where $$L_d(I)$$ is the so-called "differential inductance" and is defined as: $$L_d = \frac{d\Phi_{\mathbf{B}}}{dI}$$. In an air core inductor or a ferromagnetic core inductor below saturation, the inductance is constant (and equal to the differential inductance), so the stored energy is
 * $$W = L\int_0^{I_0} I \, dI$$

$$ For inductors with magnetic cores, the above equation is only valid for linear regions of the magnetic flux, at currents below the saturation level of the inductor, where the inductance is approximately constant. Where this is not the case, the integral form must be used with $$L_d$$ variable.

Voltage step response
When a voltage step is applied to an inductor:
 * In the short-time limit, since the current cannot change instantaneously, the initial current is zero. The equivalent circuit of an inductor immediately after the step is applied is an open circuit.
 * As time passes, the current increases at a constant rate with time until the inductor starts to saturate.
 * In the long-time limit, the transient response of the inductor will die out, the magnetic flux through the inductor will become constant, so no voltage would be induced between the terminals of the inductor. Therefore, assuming the resistance of the windings is negligible, the equivalent circuit of an inductor a long time after the step is applied is a short circuit.

Ideal and real inductors
The constitutive equation describes the behavior of an ideal inductor with inductance $$L$$, and without resistance, capacitance, or energy dissipation. In practice, inductors do not follow this theoretical model; real inductors have a measurable resistance due to the resistance of the wire and energy losses in the core, and parasitic capacitance between turns of the wire.

A real inductor's capacitive reactance rises with frequency, and at a certain frequency, the inductor will behave as a resonant circuit. Above this self-resonant frequency, the capacitive reactance is the dominant part of the inductor's impedance. At higher frequencies, resistive losses in the windings increase due to the skin effect and proximity effect.

Inductors with ferromagnetic cores experience additional energy losses due to hysteresis and eddy currents in the core, which increase with frequency. At high currents, magnetic core inductors also show sudden departure from ideal behavior due to nonlinearity caused by magnetic saturation of the core.

Inductors radiate electromagnetic energy into surrounding space and may absorb electromagnetic emissions from other circuits, resulting in potential electromagnetic interference.

An early solid-state electrical switching and amplifying device called a saturable reactor exploits saturation of the core as a means of stopping the inductive transfer of current via the core.

Q factor
The winding resistance appears as a resistance in series with the inductor; it is referred to as DCR (DC resistance). This resistance dissipates some of the reactive energy. The quality factor (or Q) of an inductor is the ratio of its inductive reactance to its resistance at a given frequency, and is a measure of its efficiency. The higher the Q factor of the inductor, the closer it approaches the behavior of an ideal inductor. High Q inductors are used with capacitors to make resonant circuits in radio transmitters and receivers. The higher the Q is, the narrower the bandwidth of the resonant circuit.

The Q factor of an inductor is defined as

 * $$Q = \frac{\omega L}{R}$$

where $$L$$ is the inductance, $$R$$ is the DC resistance, and the product $$\omega L$$ is the inductive reactance

Q increases linearly with frequency if L and R are constant. Although they are constant at low frequencies, the parameters vary with frequency. For example, skin effect, proximity effect, and core losses increase R with frequency; winding capacitance and variations in permeability with frequency affect L.

At low frequencies and within limits, increasing the number of turns N improves Q because L varies as N2 while R varies linearly with N. Similarly increasing the radius r of an inductor improves (or increases) Q because L varies with r2 while R varies linearly with r. So high Q air core inductors often have large diameters and many turns. Both of those examples assume the diameter of the wire stays the same, so both examples use proportionally more wire. If the total mass of wire is held constant, then there would be no advantage to increasing the number of turns or the radius of the turns because the wire would have to be proportionally thinner.

Using a high permeability ferromagnetic core can greatly increase the inductance for the same amount of copper, so the core can also increase the Q. Cores however also introduce losses that increase with frequency. The core material is chosen for best results for the frequency band. High Q inductors must avoid saturation; one way is by using a (physically larger) air core inductor. At VHF or higher frequencies an air core is likely to be used. A well designed air core inductor may have a Q of several hundred.

Applications
Inductors are used extensively in analog circuits and signal processing. Applications range from the use of large inductors in power supplies, which in conjunction with filter capacitors remove ripple which is a multiple of the mains frequency (or the switching frequency for switched-mode power supplies) from the direct current output, to the small inductance of the ferrite bead or torus installed around a cable to prevent radio frequency interference from being transmitted down the wire.

Inductors are used as the energy storage device in many switched-mode power supplies to produce DC current. The inductor supplies energy to the circuit to keep current flowing during the "off" switching periods and enables topographies where the output voltage is higher than the input voltage.

A tuned circuit, consisting of an inductor connected to a capacitor, acts as a resonator for oscillating current. Tuned circuits are widely used in radio frequency equipment such as radio transmitters and receivers, as narrow bandpass filters to select a single frequency from a composite signal, and in electronic oscillators to generate sinusoidal signals.

Two (or more) inductors in proximity that have coupled magnetic flux (mutual inductance) form a transformer, which is a fundamental component of every electric utility power grid. The efficiency of a transformer may decrease as the frequency increases due to eddy currents in the core material and skin effect on the windings. The size of the core can be decreased at higher frequencies. For this reason, aircraft use 400 hertz alternating current rather than the usual 50 or 60 hertz, allowing a great saving in weight from the use of smaller transformers. Transformers enable switched-mode power supplies that galvanically isolate the output from the input.

Inductors are also employed in electrical transmission systems, where they are used to limit switching currents and fault currents. In this field, they are more commonly referred to as reactors.

Inductors have parasitic effects which cause them to depart from ideal behavior. They create and suffer from electromagnetic interference (EMI). Their physical size prevents them from being integrated on semiconductor chips. So the use of inductors is declining in modern electronic devices, particularly compact portable devices. Real inductors are increasingly being replaced by active circuits such as the gyrator which can synthesize inductance using capacitors.

Inductor construction
An inductor usually consists of a coil of conducting material, typically insulated copper wire, wrapped around a core either of plastic (to create an air-core inductor) or of a ferromagnetic (or ferrimagnetic) material; the latter is called an "iron core" inductor. The high permeability of the ferromagnetic core increases the magnetic field and confines it closely to the inductor, thereby increasing the inductance. Low frequency inductors are constructed like transformers, with cores of electrical steel laminated to prevent eddy currents. 'Soft' ferrites are widely used for cores above audio frequencies, since they do not cause the large energy losses at high frequencies that ordinary iron alloys do. Inductors come in many shapes. Some inductors have an adjustable core, which enables changing of the inductance. Inductors used to block very high frequencies are sometimes made by stringing a ferrite bead on a wire.

Small inductors can be etched directly onto a printed circuit board by laying out the trace in a spiral pattern. Some such planar inductors use a planar core. Small value inductors can also be built on integrated circuits using the same processes that are used to make interconnects. Aluminium interconnect is typically used, laid out in a spiral coil pattern. However, the small dimensions limit the inductance, and it is far more common to use a circuit called a gyrator that uses a capacitor and active components to behave similarly to an inductor. Regardless of the design, because of the low inductances and low power dissipation on-die inductors allow, they are currently only commercially used for high frequency RF circuits.

Shielded inductors
Inductors used in power regulation systems, lighting, and other systems that require low-noise operating conditions, are often partially or fully shielded. In telecommunication circuits employing induction coils and repeating transformers shielding of inductors in close proximity reduces circuit cross-talk.

Air-core inductor
The term air core coil describes an inductor that does not use a magnetic core made of a ferromagnetic material. The term refers to coils wound on plastic, ceramic, or other nonmagnetic forms, as well as those that have only air inside the windings. Air core coils have lower inductance than ferromagnetic core coils, but are often used at high frequencies because they are free from energy losses called core losses that occur in ferromagnetic cores, which increase with frequency. A side effect that can occur in air core coils in which the winding is not rigidly supported on a form is 'microphony': mechanical vibration of the windings can cause variations in the inductance.

Radio-frequency inductor

At high frequencies, particularly radio frequencies (RF), inductors have higher resistance and other losses. In addition to causing power loss, in resonant circuits this can reduce the Q factor of the circuit, broadening the bandwidth. In RF inductors specialized construction techniques are used to minimize these losses. The losses are due to these effects:
 * Skin effect: The resistance of a wire to high frequency current is higher than its resistance to direct current because of skin effect.   Due to induced eddy currents, radio frequency alternating current does not penetrate far into the body of a conductor but travels along its surface.  For example, at 6 MHz the skin depth of copper wire is about 0.001 inches (25 μm); most of the current is within this depth of the surface.  Therefore, in a solid wire, the interior portion of the wire may carry little current, effectively increasing its resistance.
 * Proximity effect: Another similar effect that also increases the resistance of the wire at high frequencies is proximity effect, which occurs in parallel wires that lie close to each other. The individual magnetic field of adjacent turns induces eddy currents in the wire of the coil, which causes the current density in the conductor to be displaced away from the adjacent surfaces.  Like skin effect, this reduces the effective cross-sectional area of the wire conducting current, increasing its resistance.
 * Dielectric losses: The high frequency electric field near the conductors in a tank coil can cause the motion of polar molecules in nearby insulating materials, dissipating energy as heat. For this reason, coils used for tuned circuits may be suspended in air, supported by narrow plastic or ceramic strips rather than being wound on coil forms.
 * Parasitic capacitance: The capacitance between individual wire turns of the coil, called parasitic capacitance, does not cause energy losses but can change the behavior of the coil. Each turn of the coil is at a slightly different potential, so the electric field between neighboring turns stores charge on the wire, so the coil acts as if it has a capacitor in parallel with it. At a high enough frequency this capacitance can resonate with the inductance of the coil forming a tuned circuit, causing the coil to become self-resonant.

To reduce parasitic capacitance and proximity effect, high Q RF coils are constructed to avoid having many turns lying close together, parallel to one another. The windings of RF coils are often limited to a single layer, and the turns are spaced apart. To reduce resistance due to skin effect, in high-power inductors such as those used in transmitters the windings are sometimes made of a metal strip or tubing which has a larger surface area, and the surface is silver-plated.
 * Basket-weave coils: To reduce proximity effect and parasitic capacitance, multilayer RF coils are wound in patterns in which successive turns are not parallel but crisscrossed at an angle; these are often called honeycomb or basket-weave coils. These are occasionally wound on a vertical insulating supports with dowels or slots, with the wire weaving in and out through the slots.
 * Spiderweb coils: Another construction technique with similar advantages is flat spiral coils. These are often wound on a flat insulating support with radial spokes or slots, with the wire weaving in and out through the slots; these are called spiderweb coils. The form has an odd number of slots, so successive turns of the spiral lie on opposite sides of the form, increasing separation.
 * Litz wire: To reduce skin effect losses, some coils are wound with a special type of radio frequency wire called litz wire. Instead of a single solid conductor, litz wire consists of a number of smaller wire strands that carry the current. Unlike ordinary stranded wire, the strands are insulated from each other, to prevent skin effect from forcing the current to the surface, and are twisted or braided together. The twist pattern ensures that each wire strand spends the same amount of its length on the outside of the wire bundle, so skin effect distributes the current equally between the strands, resulting in a larger cross-sectional conduction area than an equivalent single wire.

Small inductors for low current and low power are made in molded cases resembling resistors. These may be either plain (phenolic) core or ferrite core. An ohmmeter readily distinguishes them from similar-sized resistors by showing the low resistance of the inductor.
 * Axial Inductor

Ferromagnetic-core inductor

Ferromagnetic-core or iron-core inductors use a magnetic core made of a ferromagnetic or ferrimagnetic material such as iron or ferrite to increase the inductance. A magnetic core can increase the inductance of a coil by a factor of several thousand, by increasing the magnetic field due to its higher magnetic permeability. However the magnetic properties of the core material cause several side effects which alter the behavior of the inductor and require special construction: Core losses:A time-varying current in a ferromagnetic inductor, which causes a time-varying magnetic field in its core, causes energy losses in the core material that are dissipated as heat, due to two processes: Eddy currents:From Faraday's law of induction, the changing magnetic field can induce circulating loops of electric current in the conductive metal core. The energy in these currents is dissipated as heat in the resistance of the core material. The amount of energy lost increases with the area inside the loop of current. Hysteresis:Changing or reversing the magnetic field in the core also causes losses due to the motion of the tiny magnetic domains it is composed of. The energy loss is proportional to the area of the hysteresis loop in the BH graph of the core material. Materials with low coercivity have narrow hysteresis loops and so low hysteresis losses. Core loss is non-linear with respect to both frequency of magnetic fluctuation and magnetic flux density. Frequency of magnetic fluctuation is the frequency of AC current in the electric circuit; magnetic flux density corresponds to current in the electric circuit. Magnetic fluctuation gives rise to hysteresis, and magnetic flux density causes eddy currents in the core. These nonlinearities are distinguished from the threshold nonlinearity of saturation. Core loss can be approximately modeled with Steinmetz's equation. At low frequencies and over limited frequency spans (maybe a factor of 10), core loss may be treated as a linear function of frequency with minimal error. However, even in the audio range, nonlinear effects of magnetic core inductors are noticeable and of concern. Saturation:If the current through a magnetic core coil is high enough that the core saturates, the inductance will fall and current will rise dramatically. This is a nonlinear threshold phenomenon and results in distortion of the signal. For example, audio signals can suffer intermodulation distortion in saturated inductors. To prevent this, in linear circuits the current through iron core inductors must be limited below the saturation level. Some laminated cores have a narrow air gap in them for this purpose, and powdered iron cores have a distributed air gap. This allows higher levels of magnetic flux and thus higher currents through the inductor before it saturates. Curie point demagnetization:If the temperature of a ferromagnetic or ferrimagnetic core rises to a specified level, the magnetic domains dissociate, and the material becomes paramagnetic, no longer able to support magnetic flux. The inductance falls and current rises dramatically, similarly to what happens during saturation. The effect is reversible: When the temperature falls below the Curie point, magnetic flux resulting from current in the electric circuit will realign the magnetic domains of the core and its magnetic flux will be restored. The Curie point of ferromagnetic materials (iron alloys) is quite high; iron is highest at 770°C. However, for some ferrimagnetic materials (ceramic iron compounds – ferrites) the Curie point can be close to ambient temperatures (below 100°C).

Laminated-core inductor
Low-frequency inductors are often made with laminated cores to prevent eddy currents, using construction similar to transformers. The core is made of stacks of thin steel sheets or laminations oriented parallel to the field, with an insulating coating on the surface. The insulation prevents eddy currents between the sheets, so any remaining currents must be within the cross sectional area of the individual laminations, reducing the area of the loop and thus reducing the energy losses greatly. The laminations are made of low-conductivity silicon steel to further reduce eddy current losses.

Ferrite-core inductor
For higher frequencies, inductors are made with cores of ferrite. Ferrite is a ceramic ferrimagnetic material that is nonconductive, so eddy currents cannot flow within it. The formulation of ferrite is xxFe2O4 where xx represents various metals. For inductor cores soft ferrites are used, which have low coercivity and thus low hysteresis losses.

Powdered-iron-core inductor
Another material is powdered iron cemented with a binder. Medium frequency equipment almost exclusively uses powdered iron cores, and inductors and transformers built for the lower shortwaves are made using either cemented powdered iron or ferrites.

Toroidal-core inductor

In an inductor wound on a straight rod-shaped core, the magnetic field lines emerging from one end of the core must pass through the air to re-enter the core at the other end. This reduces the field, because much of the magnetic field path is in air rather than the higher permeability core material and is a source of electromagnetic interference. A higher magnetic field and inductance can be achieved by forming the core in a closed magnetic circuit. The magnetic field lines form closed loops within the core without leaving the core material. The shape often used is a toroidal or doughnut-shaped ferrite core. Because of their symmetry, toroidal cores allow a minimum of the magnetic flux to escape outside the core (called leakage flux), so they radiate less electromagnetic interference than other shapes. Toroidal core coils are manufactured of various materials, primarily ferrite, powdered iron and laminated cores.

Variable inductor

Probably the most common type of variable inductor today is one with a moveable ferrite magnetic core, which can be slid or screwed in or out of the coil. Moving the core farther into the coil increases the permeability, increasing the magnetic field and the inductance. Many inductors used in radio applications (usually less than 100 MHz) use adjustable cores in order to tune such inductors to their desired value, since manufacturing processes have certain tolerances (inaccuracy). Sometimes such cores for frequencies above 100 MHz are made from highly conductive non-magnetic material such as aluminum. They decrease the inductance because the magnetic field must bypass them.

Air core inductors can use sliding contacts or multiple taps to increase or decrease the number of turns included in the circuit, to change the inductance. A type much used in the past but mostly obsolete today has a spring contact that can slide along the bare surface of the windings. The disadvantage of this type is that the contact usually short-circuits one or more turns. These turns act like a single-turn short-circuited transformer secondary winding; the large currents induced in them cause power losses.

A type of continuously variable air core inductor is the variometer. This consists of two coils with the same number of turns connected in series, one inside the other. The inner coil is mounted on a shaft so its axis can be turned with respect to the outer coil. When the two coils' axes are collinear, with the magnetic fields pointing in the same direction, the fields add and the inductance is maximum. When the inner coil is turned so its axis is at an angle with the outer, the mutual inductance between them is smaller so the total inductance is less. When the inner coil is turned 180° so the coils are collinear with their magnetic fields opposing, the two fields cancel each other and the inductance is very small. This type has the advantage that it is continuously variable over a wide range. It is used in antenna tuners and matching circuits to match low frequency transmitters to their antennas.

Another method to control the inductance without any moving parts requires an additional DC current bias winding which controls the permeability of an easily saturable core material. See Magnetic amplifier.

Choke
A choke is an inductor designed specifically for blocking high-frequency alternating current (AC) in an electrical circuit, while allowing DC or low-frequency signals to pass. Because the inductor restricts or "chokes" the changes in current, this type of inductor is called a choke. It usually consists of a coil of insulated wire wound on a magnetic core, although some consist of a donut-shaped "bead" of ferrite material strung on a wire. Like other inductors, chokes resist changes in current passing through them increasingly with frequency. The difference between chokes and other inductors is that chokes do not require the high Q factor construction techniques that are used to reduce the resistance in inductors used in tuned circuits.

Circuit analysis
The effect of an inductor in a circuit is to oppose changes in current through it by developing a voltage across it proportional to the rate of change of the current. An ideal inductor would offer no resistance to a constant direct current; however, only superconducting inductors have truly zero electrical resistance.

The relationship between the time-varying voltage v(t) across an inductor with inductance L and the time-varying current i(t) passing through it is described by the differential equation:

 * $$v(t) = L \frac{di(t)}{dt}$$

When there is a sinusoidal alternating current (AC) through an inductor, a sinusoidal voltage is induced. The amplitude of the voltage is proportional to the product of the amplitude ($$I_P$$) of the current and the angular frequency ($$\omega$$) of the current.

 * $$\begin{align}

i(t) &= I_\mathrm P \sin(\omega t) \\ \frac{di(t)}{dt} &= I_\mathrm P \omega \cos(\omega t) \\ v(t) &= L I_\mathrm P \omega \cos(\omega t) \end{align}$$

In this situation, the phase of the current lags that of the voltage by π/2 (90°). For sinusoids, as the voltage across the inductor goes to its maximum value, the current goes to zero, and as the voltage across the inductor goes to zero, the current through it goes to its maximum value.

If an inductor is connected to a direct current source with value I via a resistance R (at least the DCR of the inductor), and then the current source is short-circuited, the differential relationship above shows that the current through the inductor will discharge with an exponential decay:

 * $$i(t) = I e^{-\frac{R}{L}t}$$

Reactance
The ratio of the peak voltage to the peak current in an inductor energised from an AC source is called the reactance and is denoted XL.

 * $$X_\mathrm L = \frac {V_\mathrm P}{I_\mathrm P} = \frac {\omega L I_\mathrm P}{I_\mathrm P} $$

Thus,

 * $$X_\mathrm L = \omega L $$

where ω is the angular frequency.

Reactance is measured in ohms but referred to as impedance rather than resistance; energy is stored in the magnetic field as current rises and discharged as current falls. Inductive reactance is proportional to frequency. At low frequency the reactance falls; at DC, the inductor behaves as a short circuit. As frequency increases the reactance increases and at a sufficiently high frequency the reactance approaches that of an open circuit.

Corner frequency
In filtering applications, with respect to a particular load impedance, an inductor has a corner frequency defined as:

 * $$f_\mathrm{3\,dB} = \frac{R}{2\pi L}$$

Laplace circuit analysis (s-domain)
When using the Laplace transform in circuit analysis, the impedance of an ideal inductor with no initial current is represented in the s domain by:
 * $$Z(s) = Ls\, $$

where
 * $$L$$ is the inductance, and
 * $$s$$ is the complex frequency.

If the inductor does have initial current, it can be represented by: • adding a voltage source in series with the inductor, having the value:
 * $ L I_0 \,$

where
 * $L$ is the inductance, and
 * $I_0$ is the initial current in the inductor.

(The source should have a polarity that is aligned with the initial current.)

• or by adding a current source in parallel with the inductor, having the value:
 * $ \frac{I_0}{s} $

where
 * $I_0$ is the initial current in the inductor.
 * $s$ is the complex frequency.

Inductor networks
Inductors in a parallel configuration each have the same potential difference (voltage). To find their total equivalent inductance (Leq):

 * [[Image:inductors in parallel.svg|A diagram of several inductors, side by side, both leads of each connected to the same wires]]

 * $$ \frac{1}{L_\mathrm{eq}} = \frac{1}{L_1} + \frac{1}{L_2} + \cdots + \frac{1}{L_n}$$

The current through inductors in series stays the same, but the voltage across each inductor can be different. The sum of the potential differences (voltage) is equal to the total voltage. To find their total inductance:

 * [[Image:inductors in series.svg|A diagram of several inductors, connected end to end, with the same amount of current going through each]]

 * $$ L_\mathrm{eq} = L_1 + L_2 + \cdots + L_n \,\! $$

These simple relationships hold true only when there is no mutual coupling of magnetic fields between individual inductors.

Mutual inductance
Mutual inductance occurs when the magnetic field of an inductor induces a magnetic field in an adjacent inductor. Mutual induction is the basis of transformer construction.
 * $$ M = \sqrt{L_1L_2} $$

where M is the maximum mutual inductance possible between 2 inductors and L1 and L2 are the two inductors. In general
 * $$ M \leq \sqrt{L_1L_2} $$

as only a fraction of self flux is linked with the other. This fraction is called "Coefficient of flux linkage (K)" or "Coefficient of coupling".
 * $$ M = K\sqrt{L_1L_2} $$

Inductance formulas
The table below lists some common simplified formulas for calculating the approximate inductance of several inductor constructions.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Inductor


text:
Talk:Insulin

Wiki Education Foundation-supported course assignment
This article is or was the subject of a Wiki Education Foundation-supported course assignment. Further details are available on the course page. Student editor(s): Carmenmilagros.

Above undated message substituted from Template:Dashboard.wikiedu.org assignment by PrimeBOT (talk) 00:35, 17 January 2022 (UTC)

Merge articles
This article should be merged with the other language articles. There are two different Q wikipedia items Check these ones: https://es.wikipedia.org/wiki/Insulina https://en.wikipedia.org/wiki/Insulin You can't go through them through the Languages tabs! — Preceding unsigned comment added by Adam080 (talk • contribs) 23:16, 8 February 2020 (UTC)

metabolism of carbs and "fats"?
"It regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from the blood to skeletal muscles and fat tissue and by causing fat to be stored rather than used for energy."

Insulin regulates the metabolism of fat? And carbohydrates? OK, i'm no scientist. But i thought insulin regulated the distribution of glucose. Could someone please take a look at this and verify or correct. ThankeeLonginus876 (talk) 14:47, 2 July 2015 (UTC)

Numerical error in Insulin article.
In the fourth paragraph of the article, it is stated that insulin is a protein of 110 amino acid residues, with a molecular mass of 5808 Da. It is preproinsulin that has a polypeptide length of 110 residues, and a molecular mass closer to 12,500 Da. After proteolytic processing prior to secretion, the active hormone insulin is composed of 51 residues in two chains crosslinked by cystine residues. The isotope-average molecular mass of the 51-residue insulin monomer is very close to 5808. 128.2.226.68 (talk) 15:42, 28 January 2016 (UTC)

CAN WE TALK INSULINE AS A ALCOHOL — Preceding unsigned comment added by 27.131.14.26 (talk) 08:07, 31 July 2016 (UTC)

Errors in discussion on Type 1 and 2 diabetes
Was briefly reading through the article when I located what I believe to be erroneous statements:

'''When the pancreatic beta cells are destroyed by an autoimmune process, insulin can no longer be synthesized or be secreted into the blood. This results in type 2 diabetes mellitus...'''

In type 1 diabetes mellitus the destruction of beta cells is less pronounced than in type 2 diabetes, and probably not due to an autoimmune process.

These statements are mixed up for Type 1 and 2 diabetes as far as I understand. There may be even more errors, a full review of the Insulin article by subject matter expert is highly recommended.

FinalStage (talk) 16:25, 29 August 2016 (UTC)

 * This error seems to have been fixed now as I just looked at the article on October 25 2018. Vorbee (talk) 15:50, 25 October 2018 (UTC)

Intranasal insulin should get its own header/section I believe
I believe a new header should be added titled "Intranasal Insulin" as Intranasal Insulin has differing effects as traditional routes of administration for insulin.

It is important for people to know how Intranasal Insulin differs from subcutaneous injections. For example Intranasal Insulin has been researched to not cause hypoglycemia (source: https://www.ncbi.nlm.nih.gov/pubmed/23107220) and does not affect systemic glucose control (source: https://www.ncbi.nlm.nih.gov/pubmed/24101698). --CuriousGeorge16 (talk) 02:46, 23 January 2017 (UTC)

Question: Since this article has been critiqued as too long and unfocused does anyone agree that Intranasal Insulin should be briefly discussed here and linked to a new wikipedia article titled "Intranasal Insulin"? link to credible research studies on Intranasal Insulin here — Preceding unsigned comment added by CuriousGeorge16 (talk • contribs) 02:51, 23 January 2017 (UTC)

Expand on Inhaled Insulin?
There was only one mention of inhaled Insulin on this page. Do you guys think it would be beneficial to add that inhaled insulin has been linked to cancer or has at least been shown to be dangerous? (source here

Also I think we should distinguish between Inhaled Insulin and Intranasal Insulin as they seem similar to the layman but have vastly different effects and safety profiles. --CuriousGeorge16 (talk) 02:56, 23 January 2017 (UTC)

Regulation of the insulin gene
There is material at Draft:Regulation of the insulin gene which could possibly be used to expand the "Regulation" section or be made into a stand-alone article Noyster (talk),  09:12, 18 November 2017 (UTC)

Economics of insulin
Clearly insulin is a necessary good for those who need it so ordinary price elasticity does not apply. However, the availability of competing brands and formulations mean that substitute goods should provide some elasticity. Does anyone have a marketplace explanation for the high price of insulin in today's marketplace in the USA? EdEveridge (talk) 19:18, 4 April 2019 (UTC)
 * This was linked from Hacker News:
 * HN thread:
 * 173.228.123.207 (talk) 03:23, 26 June 2019 (UTC)

Source help needed
I'm sure you are correct in saying "The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin in 1969". I'm just not seeing the source. Macdonald-ross (talk) 08:26, 4 May 2022 (UTC)

A sentence on Khadria, et al.
Using insulin lispro, in 2022, after 100 years since insulin was discovered, collaborative research between California Institute of Technology and Eli Lilly and Company first reported the diffusion of insulin in a live animal.

Hi all, I see a bit of back and forth between an IP,, , and on whether to include a sentence (above) highlighting this paper in Molecular Metabolism in the article. My opinion is that we should not. Relevant policies are WP:NOTNEWS, which says "Wikipedia is not written in news style," and "breaking news should not be emphasized or treated differently from other information"; and WP:DUE which guides us to "represent all significant viewpoints... in proportion to the prominence of each viewpoint in the published reliable sources." If this paper starts getting mentioned in reviews on insulin (or the history of work on insulin) we'll mention it here. Until then, I think it's premature. I figured instead of reverting the addition again, I'd open a thread here for folks to share their thoughts. Ajpolino (talk) 16:13, 31 July 2022 (UTC)
 * My revert was not based on MEDRS, it was one of a single editor mass–adding different cites with a common author. To me that fell into a potential self–promotion or at least a COI. As with anything, a knowledgeable reviewer could reinclude them as warranted. Based on above, it does not look ready for inclusion.-- ☾Loriendrew☽  ☏(ring-ring)  17:25, 31 July 2022 (UTC)
 * I appreciate the guidance and discussion and agree with the consensus. Thanks @Ajpolino& @Loriendrew Ushistorygeek (talk) 19:40, 1 August 2022 (UTC)

Medical Uses: Ad?
The paragraph is written like an ad, by over emphasizing the features and seems out of place in the section.

The Dispovan Single-Use Pen Needle by HMD is India’s first insulin pen needle that makes self-administration easy. Featuring extra-thin walls and a multi-bevel tapered point, these pen needles prioritise patient comfort by minimising pain and ensuring seamless medication delivery. The product aims to provide affordable Pen Needles to the developing part of the country through its wide distribution channel. Additionally, the universal design of these needles guarantees compatibility with all insulin pens. 107.0.117.66 (talk) 19:44, 20 November 2023 (UTC)

 * Sounds like they just copied a description of it from the marketing website for the product. Definitely biased, that's for sure. VoidHalo (talk) 14:09, 4 July 2024 (UTC)

title: Talk:Insulin