INSULIN

From Big Medical Encyclopedia

INSULIN (Latin insula the island, an island) — hormone of a pancreas; treats group of belkovopeptidny hormones.

In 1900 L. V. Sobolev proved that islets of Langerhans pancreas (see) are the place of formation of the substance regulating carbohydrate metabolism in an organism. In 1921 F. Banting and Best (S. N. of Best) received the extract from insular tissue of a pancreas containing insulin. In 1925. And. it was received in a crystal look. In 1955 F. Sanger studied the amino-acid sequence and established structure And. cattle and pigs.

The relative molecular mass of monomer P. — apprx. 6000. Molecule I. contains 51 amino acids and consists of two chains; the chain with N-trailer glycine is called the A-chain and consists of 21 amino acids, the second — a B-chain — consists of 30 amino acids. And - and B-chains are connected by a disulfide bridge, integrity a cut plays a large role in preservation biol, activities of a molecule I. (a formula see below).

Molecule of insulin of the person

It is closest on amino-acid structure to And. person I. pigs, the molecule to-rogo differs only on one amino acid in a B-chain (instead of threonine in the 30th situation there is an alanine).

Biosynthesis of insulin, regulation of secretion of insulin

And. it is synthesized in basphilic insulotsita (beta cells) of islets of Langerhans of a pancreas from the predecessor — pro-insulin. For the first time pro-insulin was found by D. F. Steiner in the late sixties Proinsulin — one-chained polypeptide with relative a pier. weight apprx. 10 000, contains more than 80 amino acids. Pro-insulin represents the molecule P. as if closed by peptide which was called connecting, or C-peptide; this peptide does a molecule I. biologically inactive. On immunol, pro-insulin is close to the characteristic to I. Proinsulin is synthesized on ribosomes of insulotsit, then on tanks of a cytoplasmic reticulum the molecule of pro-insulin moves to a lamellar complex (Golgi's complex), from to-rogo again formed secretory granules containing pro-insulin separate. In secretory granules under the influence of enzymes from pro-insulin S-peptide separates and it is formed And. Process of enzymatic transformation of pro-insulin proceeds century several stages as a result of which insulin, intermediate forms of pro-insulin and S-peptide is formed. All these substances possess different biol, and immune activity and can participate in regulation of different types of a metabolism. Disturbance of processes of transformation of pro-insulin in And. leads to change of a ratio of these substances, emergence of abnormal forms I. willows result of it is to shift in regulation of a metabolism.

Intake of hormones in blood is regulated by several mechanisms, one of which for And. (a starting signal) increase in content of glucose in blood is (see. Hyperglycemia ); an important role in regulation of receipt And. belongs to microelements, to hormones went. - kish. path (generally to secretin), to amino acids, and also c. N of page (see. Hormones ).

Transformation of insulin in an organism

At an exit in a bed of blood part I. forms complexes with proteins of a blood plasma — so-called connected insulin, other part remains in the form of free insulin. L. K. Staroseltseva and sotr. (1972) established, that there are two forms connected And.: one form — a complex I. with transferrin, another — a complex I. with one of components of alpha globulins of blood serum. Free and connected And. are excellent from each other on biol., immune and physical. - to chemical properties, and also on influence on fatty and muscular fabrics which are target organs and are called insulinchuvstvitelny and fabrics. Free And. reacts with antibodies to crystal P., stimulates absorption of glucose muscular and to some extent with fatty tissue. Connected And. does not react with antibodies to crystal P., stimulates absorption of glucose with fatty tissue and practically does not influence this process in muscular tissue. Connected And. differs from free in the speed of metabolism, behavior in the electrophoretic field, at a gelfiltration and dialysis.

At extraction of blood serum muriatic ethanol received substance, on biol, to effects similar I. Odnako is substance did not react with the antibodies received to crystal P. and therefore it was called «not suppressed insulinopodobny activity of plasma», or «insulinopodobny substance». The great value is attached to studying of insulinopodobny activity; «not suppressed insulinopodobny activity of plasma» is considered by many authors as one of forms I. Thanks to processes of binding And. with serum proteins its delivery to fabrics is provided. Besides, connected And. is as if a form of storage of hormone in blood and creates a reserve active And. in line with blood. Certain ratio free and connected And. provides normal life activity of an organism.

Quantity And., circulating in line with blood, is defined not only by the speed of secretion, but also speed of his metabolism in peripheral fabrics and bodies. Most actively processes of metabolism And. proceed in a liver. There are several assumptions of the mechanism of these processes in a liver; it is established that there are two stages — recovery of disulfide bridges in a molecule of insulin and proteolysis with formation of biologically inactive peptide fragments and amino acids. There are several insulininaktiviruyushchy and insulindegradiruyushchy fermental systems participating in I. K metabolism by it the insulininaktiviruyushchy fermental system [proteindisulfidny reductase (glutathione)] and insulindegradiruyushchy fermental system belong, edges it is presented by three types of proteolytic enzymes. Effect of proteindisulfidny reductase is resulted by recovery — S — S-bridges and education And - and B-chains And. with their subsequent proteolysis to separate peptides and amino acids. In addition to a liver, metabolism And. occurs in muscular and fatty fabrics, kidneys, a placenta. Speed of processes of metabolism can serve as control of level active And. also plays a large role in a pathogeny of a diabetes mellitus. Period biol, half-decay And. the person — apprx. 30 min.

Biological effect of insulin

And. is universal anabolic hormone. One of the brightest effects And. — its hypoglycemic action. And. exerts impact on all types of a metabolism: stimulates transport of substances through cellular membranes, promotes utilization of glucose and formation of a glycogen, inhibits a gluconeogenesis (see. Glycolysis ), brakes a lipolysis and activates a lipogenesis (see. Lipometabolism ), increases intensity of synthesis of protein. And., providing normal oxidation of glucose in a tricarbonic acid cycle (lungs, muscles, kidneys, a liver), promotes formation of makroergichesky connections (in particular, ATP) and to maintenance of the energy balance of cells. And, it is necessary for growth and development of an organism (works in a synergism with somatotropic hormone of a hypophysis).

In total biol, effects And. are independent and independent from each other, however in fiziol, conditions a final effect And. it consists of direct stimulation of biosynthetic processes and simultaneous supply of cells with «construction» material (e.g., amino acids) and energy (glucose). Diverse effects And. also signal transmissions (information) in a cell to the corresponding fermental systems are implemented by its interaction with receptors of cellular membranes.

Fiziol, antagonist I. in regulation of carbohydrate metabolism and providing an organism of level of glucose, optimum for life activity, in blood is glucagon (see), and also some other hormones (thyroid gland, adrenal glands, somatotropic hormone).

Disturbances in synthesis and secretion of insulin can be different character and have various origin. So, insufficiency of secretion And. leads to a hyperglycemia and development of a diabetes mellitus (see. diabetes mellitus, etiology and pathogeny ). Excess education And. it is observed, e.g., at a hormonal and active tumor, coming from beta cells of pancreatic islands (see. Insuloma ), it is also expressed clinically by symptoms hyper dysinsulinism (see).

Methods of definition of insulin

Methods of definition of insulin can conditionally be divided on biological and radio immune. Biol, methods are based on stimulation of absorption of glucose by insulinchuvstvitelny fabrics under action And. For biol, a method the phrenic muscle and epididymidal fatty tissue received from rats of pure lines is used. Crystal And. or the studied blood serum of the person and drugs of a phrenic muscle or epididimalyyuy fatty tissue (it is better the isolated lipoblasts received from epididymidal fatty tissue) in the buffer solution containing a certain concentration of glucose are located in an incubator. On degree poglo shcheniye of glucose fabric and according to a decrease it from the incubated environment calculate contents And. in blood, using at the same time a standard curve.

Free form I. strengthens absorption of glucose generally on a phrenic muscle, about a cut the connected form I practically does not react., therefore, using a phrenic method, it is possible to define quantity free And. Absorption of glucose epididymidal fatty tissue is stimulated in the basic with the connected form I.; but with fatty tissue can partially react and free And., therefore it is possible to call the data received at an incubation with fatty tissue the general insulinny activity. Fiziol, levels free and connected And. fluctuate in very wide limits that, probably, is connected with individual type of hormonal regulation of exchange processes, and can average normal 150 — 200 mked/ml free And. and 250 — 400 mked/ml connected And.

Radio immune method of definition And. it is based on the competition marked and not marked And. in reaction with an antibody to And. in the analyzed test. Quantity radioactive And., connected with antibodies, will be in inverse proportion to concentration And. in the analyzed test. The double-antibody method which can conditionally (schematically) be presented as follows was the most successful option of a radio immune method. Antibodies against And. receive on Guinea pigs (a so-called antibody of the first order) and connect them with marked And. (1251). The received complex is repeatedly connected to the antibodies of the second order (received from a rabbit). It provides stability of a complex and a possibility of substitution reaction marked And. on not marked. As a result of this reaction not marked And. contacts antibodies, and marked And. passes into free solution.

Numerous modifications of this method are based on a stage of department marked And. from a complex with not marked And. The double-antibody method is the basis for preparation of ready sets for a radio immune method of definition And. (firms of England and France).

Drugs of insulin

For the medical purposes I. receive from a pancreas of cattle, pigs and whales. Activity And. determine biol, way (by ability to lower a sugar content in blood at healthy rabbits). For the unit of action (UA), or the international unit (IU), accept activity of 0,04082 mg of crystal insulin (standard). And. easily connects to bivalent metals, especially to zinc, cobalt, cadmium, and can form complexes with polypeptides, in particular with protamin. This property was used during creation of drugs I. the prolonged action.

On duration of action distinguish three types of drugs I. Drug of short action (apprx. 6 hours) is insulin of domestic production (And. cattle and pigs). Drug of average duration of action (10 — 12 hours) — suspension zinc-insulin amorphous — the domestic drug similar to foreign drug to a seven-tape. Insulin-protamin (18 — 24 hours), suspension zinc-insulin (to 24 hours), suspension zinc-insulin crystal belong to drugs of long action protamin-zinc-insulin for injections (16 — 20 hours of action), suspension (to 30 — 36 hours of action).

Pharmakol, the characteristic of the most used drugs I. and forms of their release — see. Hormonal drugs, table .

Indications and contraindications

And. is specific antidiabetic means and it is applied generally at a diabetes mellitus; the absolute indication is existence of ketoacidosis and a diabetic coma. The choice of drug and its dosage depend on a form and weight of disease, age and the general condition of the patient. Selection of doses and treatment And. it is carried out under control of a sugar content to blood and in urine and overseeing by a condition of the patient. Overdose And. threatens with sharp falling of a sugar content in blood, a hypoglycemic coma. Specific indications to use of these or those drugs I. at a diabetes mellitus at adults and children — see. diabetes mellitus, treatment .

Drugs I. are applied to treatment of some mental diseases. In the USSR insulinoshokovy treatment of schizophrenia was applied in 1936. A.S. Kronfeld and E. Ya. Shternberg. With the advent of neuroleptics treatment And. became method of the choice — see. Schizophrenia .

In small doses And. sometimes appoint at the general exhaustion, a furunculosis, vomiting of pregnant women, hepatitises, etc.

All drugs I. the prolonged action enter only under skin (or intramusculary). Intravenously (e.g., at a diabetic coma) it is possible to enter only solution of insulin crystal for injections. It is impossible to enter suspensions zinc-insulin (and other drugs I. the prolonged action) in one syringe with solution of insulin for injections; in case of need enter solution of insulin for injections the separate syringe.

Contraindication — an allergy to And.; relative contraindications — the diseases proceeding with a hypoglycemia. Care at treatment is necessary And. patients at whom coronary insufficiency and disturbances of cerebral circulation are observed.



Bibliography: Biochemistry of hormones and hormonal regulation, under the editorship of N. A. Yudayev, page 93, M., 1976; Nyyuskholm E. I Start To. Regulation of metabolism, the lane with English, page 387, etc., M., 1977; Problems of medical enzymology, under the editorship of G. R. Mardasheva, page 40, M., 1970, bibliogr.; The guide to clinical endocrinology, under the editorship of V. G. Baranov, L., 1977; The Diabetes mellitus, under the editorship of V. R. Klyachko, page 130, M., 1974; Staroseltseva L. K. Various forms of insulin in an organism and their biological value, in book: Sovr. vopr, endocrinins., under the editorship of H. A. Yudayeva, century 4, page 123, M., 1972; Yudayev N. A. Biochemistry of hormonal regulation of a metabolism, Vestn. Academy of Sciences of the USSR, JVa 11, page 29, 1974; Banting F. G., and. In e s t of Page H. Internal secretion of pancreas, J. Lab. clin. Med., v. 7, p. 251, 1922; Cerasi E. Luft R. Diabetes mellitus — a disorder of cellular information transmission, Horm. metaboi. Res., v. 4, p. 246, 1970, bibliogr.; Insulin, ed. by R. Luft, Gentofte, 1976; Steiner D. F. a, o. Proinsulin and the biosynthesis of insulin, Recent Progr. Hormone Res., v. 25, p. 207, 1969, bibliogr.

V. S. Ilyin, L. K. Staroseltseva

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