insulin, hormone hormone, secretory substance carried from one gland or organ of the body via the bloodstream to more or less specific tissues, where it exerts some influence upon the metabolism of the target tissue.
..... Click the link for more information. secreted by the β cells of the islets of Langerhans, specific groups of cells in the pancreas pancreas (păn`krēəs), glandular organ that secretes digestive enzymes and hormones.
..... Click the link for more information. . Insufficiency of insulin in the body results in diabetes diabetes or diabetes mellitus (məlī`təs)
..... Click the link for more information. . Insulin was one of the first products to be manufactured using genetic engineering genetic engineering, the use of various methods to manipulate the DNA (genetic material) of cells to change hereditary traits or produce biological products.
..... Click the link for more information. .

Action

In general, insulin acts to reduce extracellular (including blood plasma) levels of glucose glucose, dextrose, or grape sugar, monosaccharide sugar with the empirical formula C₆H₁₂O₆ .
..... Click the link for more information. by interacting in some way yet unknown with various cell membranes. In adipose (fatty) tissue it facilitates the cellular uptake of glucose and its subsequent conversion to fatty acids fatty acid, any of the organic carboxylic acids present in fats and oils as esters of glycerol . Molecular weights of fatty acids vary over a wide range. The carbon skeleton of any fatty acid is unbranched. Some fatty acids are saturated, i.e.
..... Click the link for more information. , and it inhibits the breakdown of fatty acids to simpler compounds. In muscle it again facilitates the transport of glucose into cells and in addition stimulates its conversion to glycogen glycogen (glī`kəjən)
..... Click the link for more information. . It also increases protein synthesis in muscle. In the liver, insulin facilitates glucose catabolism catabolism (kətăb`əlĭz'əm), subdivision of metabolism involving all degradative chemical reactions in the living cell.
..... Click the link for more information. and its conversion to glycogen and inhibits its synthesis from simpler compounds.

Isolation and Structure

Canadians Frederick G. Banting Banting, Sir Frederick Grant, 1891–1941, Canadian physician, M.D. Univ. of Toronto, 1922. From 1923 he was professor of medical research at Toronto. Working with C. H. Best under the direction of J. J. R.
..... Click the link for more information. and Charles H. Best Best, Charles Herbert, 1899–1978, Canadian physiologist, b. West Pembroke, Maine. With F. G. Banting he discovered (1921) the use of insulin in the treatment of diabetes. He was appointed professor of physiology at the Univ.
..... Click the link for more information. were the first to obtain, from extracts of pancreas (1921–22), a preparation of insulin that could serve to replace a deficiency of the hormone in the human body. The complete amino acid sequence of the insulin molecule was described in the early 1950s; insulin was the first protein to be sequenced entirely. This pioneering work was confirmed from 1963 to 1966, when several groups reported laboratory synthesis of biologically active insulin. The three-dimensional structure of the crystalline hormone was published in 1969.

Insulin has been shown to be a protein consisting of two polypeptide chains (see peptide peptide, organic compound composed of amino acids linked together chemically by peptide bonds. The peptide bond always involves a single covalent link between the α-carboxyl (oxygen-bearing carbon) of one amino acid and the amino nitrogen of a second amino acid.
..... Click the link for more information. ), one of 21 amino acid residues and the other of 30, joined by two disulfide bridges (see cysteine cysteine (sĭs`tēn), organic compound, one of the 20 amino acids commonly found in animal proteins .
..... Click the link for more information. ). The two chains are synthesized in the β cells as part of one continuous polypeptide chain called proinsulin; a 32-amino acid sequence (the connecting peptide) is subsequently split out of the proinsulin molecule by an enzyme resembling trypsin trypsin, enzyme that acts to degrade protein ; it is often referred to as a proteolytic enzyme, or proteinase. Trypsin is one of the three principal digestive proteinases, the other two being pepsin and chymotrypsin .
..... Click the link for more information. to yield active insulin.

Insulin in Diabetes Treatment

Many, but not all, of the symptoms of diabetes can be controlled by the administration of insulin. The forms of insulin available early in the 20th cent. had to be injected frequently because they were quick-acting. Later modifications gave the insulin solution a more prolonged action so that hypodermic injections could be made less frequently. Some now control their insulin levels via a small, portable insulin pump. In certain cases of mild diabetes, oral medications that stimulate production of insulin can be taken in lieu of insulin. See glucagon glucagon (gl
..... Click the link for more information. .

insulin

Polypeptide hormone (see peptide) that regulates blood glucose levels. Secreted by the islets of Langerhans (see Langerhans, islets of) in the pancreas when blood glucose rises, as after a meal, it helps transfer the glucose into the body's cells to be oxidized (see oxidation-reduction) for energy or converted and stored as fatty acids or glycogen. When blood glucose falls, insulin secretion stops and the liver releases more glucose into the blood. Insulin has various related functions in the liver, muscles, and other tissues, controlling the balance of glucose with related compounds. Insulin-related disorders include diabetes mellitus and hypoglycemia. Frederick Banting and J.J.R. Macleod won a Nobel Prize in 1923 for discovering insulin, and Frederick Sanger won one in 1958 for determining its amino acid sequence.

Insulin

Produced and secreted by the beta cells of the islets (insulae) of Langerhans of the pancreas, the hormone which regulates the use and storage of foodstuffs, especially the carbohydrates. Chemically insulin is a small, simple protein. Insulins from various species differ in the composition; these differences account for the fact that diabetics treated with animal insulins develop antibodies which may sometimes interfere with the action of the hormone. The structure has been verified by synthesis of insulin from pure amino acids in the laboratory. See Carbohydrate metabolism, Immunology, Pancreas

Insulin, being a polypeptide, can also be broken down by many proteolytic enzymes to its constituent amino acids. Because of these breakdown systems, the turnover of insulin in the body is rapid; its “half-life” has been estimated to be 10–30 min. The liver alone is capable of destroying about 50% of the insulin passing through it on its way from the pancreas to the bodily tissues.

The role played by insulin in the body is most clearly approached by considering the abnormalities resulting from removing insulin from an organism by surgical excision of the pancreas or by the chemical destruction of the insulin-producing cells: A state of severe diabetes is produced. Normally the blood glucose level is about 100 mg/100 ml. A carbohydrate meal raises the blood sugar to about 150 mg and the premeal value is reached again within 1.5 h. The normal organism manages to dispose of food by storage and oxidation within this period because insulin is present. When food (carbohydrate and protein) reaches the upper intestine, a substance is liberated which in turn stimulates the beta cells to secrete extra insulin. Insulin acts on most tissues to speed the uptake of glucose. In the cells the glucose is burned for energy, stored as glycogen, or transformed to and stored as fat. The human pancreas probably produces 1–2 mg of the hormone per day. This is sufficient to regulate the metabolism of more than 250 g of carbohydrate, 70 g of protein, and 75 g of fat, the usual composition of an ordinary 2000-calorie diet.

In diabetes the rate of glucose uptake is slowed, the level of circulating blood sugar rises, and sugar spills over into the excreted urine. Calories are wasted, more water is excreted, and there is muscular weakness and weight loss; hence urinary frequency, hunger, thirst, and fatigue. Whenever glucose metabolism is defective, stored fat is broken down to fatty acids because of the actions of adrenaline and the pituitary growth hormone. Insulin is able to reverse all these phenomena by favoring storage and swift intake of glucose into the tissues, by decreasing the breakdown of stored fat, and by promoting protein synthesis.

When insulin is secreted or given in excess, it may lower the blood sugar level much below its normal value, causing hypoglycemia. Hypoglycemia is dangerous because the metabolism in the brain cells depends primarily upon an adequate supply of glucose.

The precise molecular mechanisms of insulin action are still not known. The initial step is the binding of the hormone to a specific receptor on the cell membrane. This event somehow activates a set of transport molecules, so that glucose, potassium, and amino acids enter cells more freely. At the same time, fat breakdown is slowed and glycogen storage increased. All these actions depend upon the integrity of the outer cell membrane. See Cell permeability

Not all the cells of the body require or respond to insulin. The insulin-responsive tissues are the liver, skeletal muscle, the heart, and the adipose tissue. Sensitivity to insulin is affected by many conditions. Obesity, antibodies to the hormone or its receptor, oversecretion of growth hormone or adrenal steroids, ketosis, and unknown genetic factors all cause insulin resistance. Muscular exercise, correction of obesity, and a deficiency of pituitary or adrenal hormones are associated with an increased sensitivity to the hormone.