GLUCAGON

From Big Medical Encyclopedia

GLUCAGON — the proteinaceous and peptide hormone participating in maintenance of carbohydrate metabolism; is a physiological antagonist of insulin, and also a stimulator of its secretion. Cosecretes alpha cells of islands of a pancreas of animals and the person.

In 1922 J. Maklaud paid attention that at intravenous administration insulin (see) the unexpected hyper glycemic effect was observed; J. Murlin in 1923 suggested that such effect is explained by existence in patent drugs of insulin of the accessory substance capable to cause hyperglycemia (see); this substance was called a glucagon. In 1950 Pinkus in an experiment showed that at destruction by mesoxalyl urea of beta cells of a pancreas G.'s education was not broken, and at introduction by an animal of the salts of cobalt striking alpha cells, G.'s maintenance in a pancreas sharply decreased. In 1953 Shtaub, Sinn and Berens (A. Staub, L. Sinn, O. of Behrens) received G. in a crystal look; in 1956 W. Bromer established his chemical structure. In 1966 Mr. of D. Vecchio established by pilot studies that G. is perceived by receptors of a cover of beta cells that stimulates release of insulin and receipt it in blood.

G.'s secretion by a pancreas is stimulated with a growth hormone of a hypophysis and corticotropic hormone, however the mechanism still is up to the end not found out.

Represents polypeptide about a pier. weighing 3485, consisting of 29 amino-acid remains. G.'s structure of the person following:

Н-Гис-Сер-Глн-Тре-Фен-Тре-Сер-Асп-Тир-Сер-Лиз-Тир-Лей-Асп-Сер-Арг-Арг-Ала-Гли-Асп-Фен-Вал-Глн-Три-Лей-Мет-Асп-Тре-ОН.

Accompanies insulin at all stages of its allocation from a pancreas and it is difficult separable at further cleaning; crystal drugs of insulin may contain from 5 to 10% of G. and even at recrystallization drugs G. contain traces of insulin. The isoelectric point of G. is at pH 7,5 — 8,0. At pH 3,0 — 4,0 it we will well dissolve and remains in biol, liquids. The pancreas contains from 5 to 10 mg of G. on 1 kg of weight of gland.

In addition to alpha cells of a pancreas, G. cosecretes argyrophil cells of a mucous membrane of a duodenum. Though on immunochemical and biol, to properties G. of a duodenum it is close to G. cosecreted by alpha cells of a pancreas, there is no identity between these kinds of hormone: enteral hormone has a bigger pier. weight and it exerts the stimulating impact on secretion of insulin. According to 1975, G. is formed also in alpha cells of a stomach and on chemical and immunol, to properties does not differ from G. cosecreted by a pancreas.

G.'s concentration in peripheral blood during the definition by an immunochemical method normal makes 0,5 — 6 mmkg/ml.

It is easily split by proteolytic enzymes — trypsin and chymotrypsin, and communications between tryptophane and a leucine, between a lysine and tyrosine, between arginine and alanine are generally terminated. Bacterial proteolytic enzymes also quickly split

G. G. collapses in many fabrics, but is the strongest — in a liver and kidneys. Time of its half-decay short, but is definitely not determined. Duration of hyper glycemic action of G. is approximately equal to duration of effect of insulin.

Biol, G.'s action in an organism occurs in three main directions: a) active participation in process of a homeostasis of glucose; b) stimulation of secretion of insulin and c) lipolytic action. The hyper glycemic effect of G. at introduction by an animal is connected with his impact on process of disintegration of a glycogen in a liver. Sharply strengthens splitting of a glycogen in a liver. It is connected with stimulation of glucagonomas of transition of an inactive form of phosphorylase B to active — phosphorylase A, edges are caused by disintegration of a glycogen to glyukozo-6-phosphate (process of a glycogenolysis — see. Glycolysis ). Glikogenolitichesky action of G. comes at its concentration 1 mmkg/ml.

Normal G. prevents the excessive decrease in glucose in blood able to occur during the strengthening of secretion of insulin. At decrease in level of sugar in blood G.'s allocation increases, contents it in blood of veins of a pancreas increases that leads to recovery of content of glucose to initial level. Has considerably more expressed glikogenolitichesky effect, than adrenaline (see); unlike the adrenaline which is also strengthening disintegration of a glycogen in a liver, G. does not influence disintegration of a glycogen in muscles.

It is established that fiziol, G.'s action is double: as antagonist and as secretagogue of insulin. At G.'s introduction to a vein at animals strengthening of insulin in blood prior to the beginning of a hyperglycemia was noted, after utilization of glucose strengthening of G. in blood is noted again. In experiments it is established that G.'s secretion and increase in its concentration in blood arise only at peroral loadings glucose while intravenous loadings of such rise did not give. It is supposed that enteral G. has almost no glikogenolitichesky effect while its insulinostimuliruyushchy effect is expressed strongly. Therefore increase in concentration of G. in blood is connected with increase in secretion of enteral G., but not pancreatic.

— the lipolytic hormone mobilizing fat to - you from fatty tissue. At the same time its kontrinsulyarny effect as insulin promotes a lipogenesis is also shown. The mechanism of lipolytic action of G. is shown through system of the adenyl cyclase activating enzymes of a lipolysis.

In G.'s experiments promotes secretion of a tireokaltsiotonin and by that causes decrease in content of calcium in blood; has positive chronotropic effect on a sinoatrial rate, positive inotropic action on a myocardium, accelerates precordial and ventricular conductivity and reduces peripheric resistance a little. This influence happens irrespective of action of catecholamines and does not exert impact on beta-blockers. It activates adenyl cyclase and a glycogenolysis in a muscle of heart.

In a wedge, practice states when G.'s secretion is increased are observed. In these cases the diabetes mellitus develops (see a diabetes mellitus). Such state is observed at a tumor of alpha cells of the insular device of a pancreas — to a glucagonoma (see). There are syndromes of insufficiency of G., they are expressed by a spontaneous hypoglycemia, edges is observed at children (see. the Hypoglycemia, at children ).

On the basis of experimental data indications to G.'s use as pharm, drug are developed at heart failure, disbolism, at intoxication by a digitalis and beta-blockers, an insulin hypoglycemia, etc.

See also Proteinaceous and peptide hormones .


BibliographyKnyazev Yu. A . Glucagon, Probl, endocrinins, and gormonoter., t. 14, No. 1, page 111, 1968, bibliogr.; Lyakishev A. A. and Golikov P. A. Cardiovascular effects of a glucagon, Cardiology, No. 7, page 128, 1972, bibliogr.; F about and P. P. Glucagon, Ergebn. Physiol., Bd 60, S. 141, 1968, Bibliogr.; Labhart A. Klinik der inneren Sekretion, B. u. a., 1971; S o k a 1 J. E. Glucagon an essential hormone, Amer. J. Med., v. 41, p. 331, 1966.

A. G. Mazowiecki

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