Insulin (from Latin insula, island) is a peptide hormone secreted by β cells of islets of Langerhans in the pancreas. She, with glucagon, a major role in regulating energy substrates, which are the main glucose, fatty acids and ketone bodies. In the couple formed by insulin and glucagon, insulin has the primary role in mammals: its absence is fatal within a few months in other species, especially birds, is the reverse: glucagon is the major hormone.
Overall, the action of insulin is often summarized by its hypoglycemic effect (decrease of glucose in the blood). It is probably fair to say that insulin is secreted according to nutritional status and physical activity, so that after meals, under the influence of elevated blood glucose (the concentration of glucose in the blood), but also under the direct influence of the presence of food in the gut, insulin secretion is stimulated, allowing the storage of glucose, end products of digestion of carbohydrate foods.
Storage areas are dietary glucose muscle, adipose tissue and liver. If food abundance, insulin also stimulates the conversion of carbohydrates into fatty acids for storage in adipose tissue. In this situation of plenty food, after meals, insulin blocks the production of glucose by the liver. By putting glucose in stock food and stopping the production of glucose by the liver, lower blood sugar. In between meals, the decrease in the secretion of insulin allows the release of stocks of glucose (liver glycogenolysis) and de novo production of glucose by the liver (gluconeogenesis). The de novo production of glucose by the liver may be prolonged because it uses the muscles directly, rather than energy reserves quantitatively much greater in adipose tissue.
During prolonged fasting (beyond a few days in adults, but only a few hours in neonates and infants), the continuing decline of insulin production allows the ketone bodies, which allows savings muscle, because ketones are derived from fatty acids in adipose tissue. Insulin also has important effects on the metabolism of proteins, it inhibits protein degradation and promotes amino acid uptake, inhibits lipolysis finally.
Beyond its immediate effect on regulating the flow of substrates, insulin has effects over long-term growth, is an anabolic hormone. It is interesting to note here the strong homology between insulin and the main growth factor, insulin-like growth factor (IGF-1), or growth factor related to insulin. Insulin as a signaling molecule in the presence of food in the digestive tract can be likened to a hormone of abundance, indicating the surplus energy for growth. Insulin has anabolic effects directly, by affecting the metabolism of carbohydrates, proteins and lipids, but also indirect, through regulation of carrier protein of IGF-1.
Diabetes are diseases of the secretion of insulin. In its severest form, diabetes mellitus (or type 1 diabetes) is fatal if not treated within a few months in an array characterized by hyperglycemia, loss of muscle and adipose tissue, and mass production and non-regulated not only glucose but also of ketones is diabetic ketoacidosis. In the West, diabetes mellitus is a disease that is not fatal, thanks to the drug insulin that diabetics must inject several times a day. This is not the case in most countries of sub-Sahelian Africa where the insulin drug is often lacking.
The role of the pancreas in diabetes has been discovered by von Oskar Minkowski in 1889 in Strasbourg, where his assistant informed him that the dogs had made the day before their thirst and urine attracted flies ... The work of the physiologists of the early twentieth century, influenced by Claude Bernard, helped establish the concept of secretion by the pancreas of a substance to regulate glucose utilization. Several researchers have prepared extracts of pancreas in order to purify a sample that could have therapeutic utility in diabetes. Nicolae Paulescu was an important precursor, but its preparations were not purified somewhat usable. The best extracts were prepared by Frederick Grant Banting with the help of Charles Best, a medical student in the laboratory of John James Richard Macleod during the summer of 1921 in Toronto. The first product developed by Banting and Best, very active and very impure opened the door to treatment of diabetes through masterful job and ultra-fast J. B. Collip, a chemist, who has prepared a few weeks in relatively pure extract and use in therapy. Banting and MacLeod were the winners of the Nobel Prize in Physiology or Medicine in 1923 rewarding their work.
History has remembered the name of the first diabetic who received preparations of Banting and Best and Collip purified by one: Leonard Thompson received 11 January 1922, a first injection will decrease slightly and very transiently blood sugar, and will be followed an abscess at the injection site, due to impurities in the preparation. A few days later, the injection of a purer product has indisputable effects on blood glucose and symptoms: effectiveness of the hormone had been proven in humans.
The first insulin was purified from the pancreas of beef and pork. In the 1930s, various preparations have yielded long-acting forms of insulin crystallization in the presence of zinc or extension of time to absorption in the skin by adding protamine (NPH insulin, prepared by Hagedorn ).
Since the early 1980s, insulin is synthesized by genetically modified organisms. Most countries have abandoned the preparation of insulin from the pancreas of beef in the aftermath of the mad cow disease, although no cases of transmission of virus or prion by insulin was never observed.
Structure and production
Insulin is a hormone made up of two polypeptide chains linked by two disulfide bridges and one intrachain disulfide bond in the chain A: A chain of 21 amino acids and B chain of 30 amino amines.La structure of insulin was determined by Frederick Sanger, was the subject of the first of his two Nobel Prizes in 1958. Insulin is produced by β cells of pancreatic islets of Langerhans in the form of pre-proinsulin consists of a single peptide chain, two fragments, the signal peptide (23AA N-ter) is removed ( cretion was the destrois disulfide bonds), we obtain the pro-insulin will undergo the removal of C-peptide to become insulin (active form). Proinsulin has a structure very similar to that of two major growth factors, IGF-1 and IGF-2, and elevated levels of these hormones allow biological effects by signaling after binding to receptors other: Hypoglycemia in massive secretion of IGF-1 and IGF-2 by tumors. Insulin circulates a concentration of the order of nanomoles per liter.
Stimulation of secretion
Blood glucose filtered through the capillary pore in the lymph that bathes the β cells of islets of Langerhans. The concentration of glucose around the β cells is the same as in the blood. The cell matter by a glucose transporter GLUT2 nonsaturable (the other body cells have a receptor rapidly saturated). The concentration of intracellular glucose therefore reflects that of blood. The glucose enters the beta cell is immediately followed by its phosphorylation by a specific hexokinase, glucokinase, whose kinetic characteristics play an important role in coupling glucose / insulin (50% loss of activity of glucokinase is the cause of a particular form of diabetes, MODY-2). Glucose metabolism in β cells increases the ATP / ADP. This induces the closure of a potassium channel sensitive to the increase in the amount of ATP. If K + (potassium) stop discharging it hyperpolarizes the β cell is a cell excitability, since it has an electrical activity when the extracellular glucose concentrations above 5 mmol · l-1. This depolarization opens voltage-sensitive calcium channels: calcium enters the cell and triggers the exocytosis of vesicles containing insulin.
We traditionally distinguish insulin according to their time and their duration of action: ultra-fast, fast, slow and semi-slow or fast mix and semi slow.
The longer period of action is primarily by adding zinc or protamine in the insulin, allowing the formation of crystals or precipitates whose dissemination into the blood is much slower. The modern insulin preparations involve molecules like insulin, whose effectiveness has been preserved, but the kinetics of absorption is changed. This provides similar with the speed of movement of the subcutaneous tissue to blood is accelerated (like "fast", which lispro, aspart and glulisine) and analog whose rate of absorption is reduced by precipitation in the subcutaneous tissue, either in the presence of zinc (analog detemir) or by modifying the isoelectric point (analog glargine).
See also Diabetes Type 1