insulin (medication) insulin (medication) as a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. insulin is also used along with glucose to treat hyperkalemia (high blood potassium levels). typically it is given by injection under the skin, but some forms may also be used by injection into a vein or muscle. there are various types of insulin, suitable for various time spans. the types are often all called insulin in the broad sense, although in a more precise sense, insulin is identical to the naturally occurring molecule whereas insulin analogues have slightly different molecules that allow for modified time of action. it is on the world health organization's list of essential medicines. in 2020, regular human insulin was the 307th most commonly prescribed medication in the united states, with more than 1 million prescriptions. "insulin therapy" and "synthetic insulin" redirect here. for the psychiatric treatment, see insulin shock therapy. for the naturally occurring protein, see insulin. insulinvials of insulinclinical datatrade nameshumulin, novolin, insuman, othersahfs/drugs.commonographmedlineplusa682611license data us dailymed: humulin routes ofadministrationsubcutaneous, intravenous, intramuscular, inhalationatc codea10ad01 (who) legal statuslegal status ca: ℞-only uk: pom (prescription only) us: ℞-only / otc eu: rx-only identifierscas number9004-10-8pubchem cid70678557drugbankdb00030chemspider34999906unii438uc14ndqkeggd04477chemical and physical dataformulac257h383n65o77s6molar mass5807.63 g·mol−1density1.09 g/cm3 melting point233 °c (451 °f) insulin can be made from the pancreas of pigs or cows. human versions can be made either by modifying pig versions, or recombinant technology using mainly e. coli or saccharomyces cerevisiae. it comes in three main types: short–acting (such as regular insulin), intermediate-acting (such as neutral protamine hagedorn (nph) insulin), and longer-acting (such as insulin glargine). history insulin was first used as a medication in canada by charles best and frederick banting in 1922. this is a chronology of key milestones in the history of the medical use of insulin. for more details on the discovery, extraction, purification, clinical use, and synthesis of insulin, see insulin 1921 research on the role of pancreas in the nutritive assimilation 1922 frederick banting, charles best and james collip use bovine insulin extract in humans at connaught laboratories in toronto, canada. 1922 leonard thompson becomes the first human to be treated with insulin. 1922 james d. havens, son of former congressman james s. havens, becomes the first american to be treated with insulin. 1922 elizabeth hughes gossett, daughter of the u.s. secretary of state, becomes the first american to be (officially) treated in toronto. 1923 eli lilly produces commercial quantities of much purer bovine insulin than banting et al. had used 1923 farbwerke hoechst, one of the forerunners of today's sanofi aventis, produces commercial quantities of bovine insulin in germany 1923 hans christian hagedorn founds the nordisk insulinlaboratorium in denmark – forerunner of today's novo nordisk 1923 constance collier returns to health after being successfully treated with insulin in strasbourg 1926 nordisk receives a danish charter to produce insulin as a non-profit 1936 canadians david m. scott and albert m. fisher formulate a zinc insulin mixture at connaught laboratories in toronto and license it to novo 1936 hagedorn discovers that adding protamine to insulin prolongs the duration of action of insulin 1946 nordisk formulates isophane porcine insulin aka neutral protamine hagedorn or nph insulin 1946 nordisk crystallizes a protamine and insulin mixture 1950 nordisk markets nph insulin 1953 novo formulates lente porcine and bovine insulins by adding zinc for longer lasting insulin 1955 frederick sanger determines the amino acid sequence of insulin 1965 synthesized by total synthesis by wang yinglai, chen-lu tsou, et al. 1969 dorothy crowfoot hodgkin solves the crystal structure of insulin by x-ray crystallography 1973 purified monocomponent (mc) insulin is introduced 1973 the u.s. officially "standardized" insulin sold for human use in the u.s. to u-100 (100 units per milliliter). prior to that, insulin was sold in different strengths, including u-80 (80 units per milliliter) and u-40 formulations (40 units per milliliter), so the effort to "standardize" the potency aimed to reduce dosage errors and ease doctors' job of prescribing insulin for people. other countries also followed suit. 1978 genentech produces biosynthetic human insulin in escherichia coli bacteria using recombinant dna techniques, licenses to eli lilly 1981 novo nordisk chemically and enzymatically converts porcine to human insulin 1982 genentech synthetic human insulin (above) approved 1983 eli lilly and company produces biosynthetic human insulin with recombinant dna technology, humulin 1985 axel ullrich sequences a human cell membrane insulin receptor. 1988 novo nordisk produces recombinant biosynthetic human insulin 1996 lilly humalog "lispro" insulin analogue approved. 2000 sanofi aventis lantus insulin "glargine" analogue approved for clinical use in the us and the eu. 2004 sanofi aventis apidra insulin "glulisine" insulin analogue approved for clinical use in the us. 2006 novo nordisk levemir "detemir" insulin analogue approved for clinical use in the us. 2008 abott laboratories " freestyle navigator cgm" gets approved. 2013 the us food and drug administration (fda) requested more cardiac safety tests for insulin degludec. 2015 insulin degludec was approved by the fda in september 2015. medical uses giving insulin with an insulin pen. insulin is used to treat a number of diseases including diabetes and its acute complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. it is also used along with glucose to treat high blood potassium levels. use during pregnancy is relatively safe for the baby. insulin was formerly used in a psychiatric treatment called insulin shock therapy. side effects some side effects are hypoglycemia (low blood sugar), hypokalemia (low blood potassium), and allergic reactions. allergy to insulin affected about 2% of people, of which most reactions are not due to the insulin itself but to preservatives added to insulin such as zinc, protamine, and meta-cresol. most reactions are type i hypersensitivity reactions and rarely cause anaphylaxis. a suspected allergy to insulin can be confirmed by skin prick testing, patch testing and occasionally skin biopsy. first line therapy against insulin hypersensitivity reactions include symptomatic therapy with antihistamines. the affected persons are then switched to a preparation that does not contain the specific agent they are reacting to or undergo desensitization. cutaneous adverse effects other side effects may include pain or skin changes at the sites of injection. repeated subcutaneous injection without site rotation can lead to lipohypertrophy and amyloidomas, which manifest as firm palpable nodules under the skin. effects of early routine use early initiation of insulin therapy for the long-term management of conditions such as type 2 diabetes would suggest that the use of insulin has unique benefits, however, with insulin therapy, there is a need to gradually raise the dose and the complexity of the regimen, as well as the likelihood of developing severe hypoglycemia which is why many people and their doctors are hesitant to begin insulin therapy in the early stage of disease management. many obstacles associated with health behaviors also prevent people with type 2 diabetes mellitus from starting or intensifying their insulin treatment, including lack of motivation, lack of familiarity with or experience with treatments, and time restraints causing people to have high glycemic loads for extended periods of time prior to starting insulin therapy. this is why managing the side effects associated with long-term early routine use of insulin for type 2 diabetes mellitus can prove to be a therapeutic and behavioral challenge. principles the idealised diagram shows the fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day containing three meals. in addition, the effect of a sugar-rich versus a starch-rich meal is highlighted. amino acid sequence of insulin preparations amino acid substitutions a-chain position b-chain position sourcespecies a-8 a-10 a-21 b-28 b-29 b-30 b-31b-32 bovine ala val asn pro lys ala n/a porcine thr ile asn pro lys ala n/a human thr ile asn pro lys thr n/a aspart (novolog) thr ile asn asp lys thr n/a lispro (humalog) thr ile asn lys pro thr n/a glulisine (apidra) thr ile asn pro glu thr n/a glargine (lantus) thr ilc gly pro lys thr arg detemir(levemir) thr ile asn pro lys n/a myristic acid degludec(tresiba) thr ile asn pro lys n/a hexadecanedioic acid ala=alanine val=valine asn=asparagine pro=proline lys=lysine thr=threonine ile=isoleucine glu=glutamine gly=glycine insulin is an endogenous hormone, which is produced by the pancreas. the insulin protein has been highly conserved across evolutionary time, and is present in both mammals and invertebrates. the insulin/insulin-like growth factor signalling pathway (iis) has been extensively studied in species including nematode worms (e.g.c. elegans), flies (drosophila melanogaster) and mice (mus musculus). its mechanisms of action are highly similar across species. both type 1 diabetes and type 2 diabetes are marked by a loss of pancreatic function, though to differing degrees. people who are affected with diabetes are referred to as diabetics. many diabetics require an exogenous source of insulin to keep their blood sugar levels within a safe target range. in 1916, nicolae c. paulescu (1869–1931) succeeded in developing an aqueous pancreatic extract that normalized a diabetic dog. in 1921, he published 4 papers in the society of biology in paris centering on the successful effects of the pancreatic extract in diabetic dogs. research on the role of the pancreas in food assimilation by paulescu was published in august 1921 in the archives internationales de physiologie, liège, belgium. initially, the only way to obtain insulin for clinical use was to extract it from the pancreas of another creature. animal glands were obtainable as a waste product of the meatpacking industry. insulin was derived primarily from cows (eli lilly and company) and pigs (nordisk insulinlaboratorium). the making of eight ounces of purified insulin could require as much as two tons of pig parts. insulin from these sources is effective in humans as it is highly similar to human insulin (three amino acid difference in bovine insulin, one amino acid difference in porcine). initially, lower preparation purity resulted in allergic reactions to the presence of non-insulin substances. purity has improved steadily since the 1920s ultimately reaching purity of 99% by the mid-1970s thanks to high-pressure liquid chromatography (hplc) methods. minor allergic reactions still occur occasionally, even to synthetic "human" insulin varieties. beginning in 1982, biosynthetic "human" insulin has been manufactured for clinical use through genetic engineering techniques using recombinant dna technology. genentech developed the technique used to produce the first such insulin, humulin, but did not commercially market the product themselves. eli lilly marketed humulin in 1982. humulin was the first medication produced using modern genetic engineering techniques in which actual human dna is inserted into a host cell (e. coli in this case). the host cells are then allowed to grow and reproduce normally, and due to the inserted human dna, they produce a synthetic version of human insulin. manufacturers claim this reduces the presence of many impurities. however, the clinical preparations prepared from such insulins differ from endogenous human insulin in several important respects; an example is the absence of c-peptide which has in recent years been shown to have systemic effects itself. novo nordisk has also developed a genetically engineered insulin independently using a yeast process. according to a survey that the international diabetes federation conducted in 2002 on the access to and availability of insulin in its member countries, approximately 70% of the insulin that is currently sold in the world is recombinant, biosynthetic 'human' insulin. a majority of insulin used clinically today is produced this way, although clinical experience has provided conflicting evidence on whether these insulins are any less likely to produce an allergic reaction. adverse reactions have been reported; these include loss of warning signs that patients may slip into a coma through hypoglycemia, convulsions, memory lapse and loss of concentration. however, the international diabetes federation's position statement from 2005 is very clear in stating that "there is no overwhelming evidence to prefer one species of insulin over another" and " animal insulins remain a perfectly acceptable alternative." since january 2006, all insulins distributed in the u.s. and some other countries are synthetic "human" insulins or their analogues. a special fda importation process is required to obtain bovine or porcine derived insulin for use in the u.s., although there may be some remaining stocks of porcine insulin made by lilly in 2005