Endocrine function of the pancreas

The pancreas is located on the back wall of the abdominal cavity, behind the stomach, at the level of L1-L2 and extends from the duodenum to the spleen gates. Its length is about 15 cm, weight - about 100 g. In the pancreas, a head located in the arch of the duodenum is distinguished, the body and tail reaching the gates of the spleen and lying retroperitoneally. Blood supply of the pancreas is carried out by the splenic and upper mesenteric artery. Venous blood enters the splenic and upper mesenteric veins. The pancreas is innervated by sympathetic and parasympathetic nerves, the terminal fibers of which are in contact with the cell membrane of islet cells.

The pancreas has exocrine and endocrine function. The latter is carried out by the islets of Langerhans, which constitute about 1-3% of the gland mass (from 1 to 1.5 million). The diameter of each is about 150 μm. One island contains 80 to 200 cells. There are several of their types for the ability to secrete polypeptide hormones. A-cells produce glucagon, B-cells - insulin, D-cells - somatostatin. A number of islet cells have been discovered that can presumably produce a vasoactive interstitial polypeptide (VIP), a gastrointestinal peptide (GIP), and a pancreatic polypeptide. B cells are localized in the center of the islet, and the rest are located along its periphery. The main mass - 60% of cells - make up B cells, 25% - A-cells, 10% - D-cells, the rest - 5% of mass.

Insulin is formed in B cells from its precursor, proinsulin, which is synthesized on the ribosomes of the coarse endoplasmic reticulum. Proinsulin consists of 3 peptide chains (A, B and C). The A and B chains are connected by disulfide bridges, the C-peptide binds the A and B chains. The molecular weight of proinsulin is 9000 daltons. The synthesized proinsulin enters the Golgi apparatus, where, under the influence of proteolytic enzymes, it splits into a C-peptide molecule with a molecular weight of 3,000 daltons and an insulin molecule with a molecular weight of 6,000 daltons. The A chain of insulin consists of 21 amino acid residues, the B chain of 30, and the C peptide of 27-33. The precursor of proinsulin in the process of its biosynthesis is preproinsulin, which differs from the former by the presence of another peptide chain consisting of 23 amino acids and joining the free end of the B chain. The molecular weight of preproinsulin is 11,500 daltons. It quickly turns into proinsulin on polysomes. From the Golgi apparatus (plate complex), insulin, C-peptide and partially proinsulin enter vesicles, where the first binds to zinc and is deposited in the crystalline state. Under the influence of various stimuli, the vesicles move to the cytoplasmic membrane and release the insulin in dissolved form into precapillary space by emiocytosis.

The most potent stimulant of its secretion is glucose, which interacts with the receptors of the cytoplasmic membrane. The response of insulin to its effect is two-phase: the first phase - the fast one - corresponds to the release of the stocks of synthesized insulin (1st pool), the second - the slow one - characterizes the rate of its synthesis (2nd pool). A signal from the cytoplasmic enzyme, adenylate cyclase, is passed on to the cAMP system, which mobilizes calcium from the mitochondria, which takes part in the release of insulin. In addition to glucose, the amino acids (arginine, leucine), glucagon, gastrin, secretin, pancreosimine, gastric inhibitory polypeptide, non-irotensin, bombesin, sulfanilamide preparations, beta-adrenostimulators, glucocorticoids, STH, ACTH have a stimulating effect on the release and secretion of insulin. Suppress the secretion and release of insulin hypoglycemia, somatostatin, nicotinic acid, diazoxide, alpha-adrenostimulation, phenytoin, phenothiazines.

Insulin in the blood is in the free (immunoreactive insulin, IRI) and is bound to the plasma proteins state. Degradation of insulin occurs in the liver (up to 80%), kidneys and adipose tissue under the influence of glutathione transferase and glutathione reductase (in the liver), insulinase (in the kidneys), proteolytic enzymes (in adipose tissue). Proinsulin and C-peptide also undergo degradation in the liver, but much more slowly.

Insulin gives a multiple effect on insulin-dependent tissues (liver, muscles, fatty tissue). On renal and nervous tissues, the lens, red blood cells, it does not have a direct effect. Insulin is an anabolic hormone that enhances the synthesis of carbohydrates, proteins, nucleic acids and fat. Its effect on carbohydrate metabolism is expressed in the increase in the transport of glucose to cells of insulin-dependent tissues, stimulation of glycogen synthesis in the liver and suppression of gluconeogenesis, and glycogenolysis, which causes a decrease in blood sugar levels. The effect of insulin on protein metabolism is expressed in stimulating the transport of amino acids through the cytoplasmic membrane of cells, the synthesis of protein and inhibition of its decay. Its participation in fat metabolism is characterized by the inclusion of fatty acids in triglycerides of adipose tissue, stimulation of lipid synthesis and suppression of lipolysis.

The biological effect of insulin is due to its ability to bind to specific receptors of the cell cytoplasmic membrane. After connecting with them, the signal through the cell-enriched enzyme-adenylate cyclase - is transferred to the cAMP system, which, with the participation of calcium and magnesium, regulates protein synthesis and glucose utilization.

The basal insulin concentration, determined by radioimmunology, is 15-20 mC / ml in healthy people. After oral loading with glucose (100 g), its level after 1 hour increases by 5-10 times in comparison with the initial one. The fasting rate of insulin on an empty stomach is 0.5-1 U / h, and after meals increases to 2.5-5 U / h. Secretion of insulin increases parasympathetic and reduces sympathetic stimulation.

Glucagon is a single-chain polypeptide with a molecular weight of 3485 daltons. It consists of 29 amino acid residues. Splits in the body with the help of proteolytic enzymes. Glucagon secretion is regulated by glucose, amino acids, gastrointestinal hormones and the sympathetic nervous system. It is intensified by hypoglycemia, arginine, gastrointestinal hormones, especially pancreosimine, factors that stimulate the sympathetic nervous system (physical activity, etc.), decrease in blood sugar content in the blood.

Opiate the production of glucagon somatostatin, hyperglycemia, elevated serum levels of FFA. The content of glucagon in the blood increases with decompensated diabetes mellitus, glucagonome. The half-life of glucagon is 10 minutes. It is inactivated mainly in the liver and kidneys by splitting into inactive fragments under the influence of enzymes carboxypeptidase, trypsin, chemotrypsin, etc.

The main mechanism of action of glucagon is characterized by an increase in the production of glucose by the liver by stimulating its decay and activation of gluconeogenesis. Glucagon binds to the hepatocyte membrane receptors and activates the enzyme adenylate cyclase, which stimulates the formation of cAMP. In this case, the active form of phosphorylase, which participates in the process of gluconeogenesis, accumulates. In addition, the formation of key glycolytic enzymes is suppressed and the release of enzymes involved in the process of gluconeogenesis is stimulated. Another glucagon-dependent tissue is fat. Linking to adipocyte receptors, glucagon promotes the hydrolysis of triglycerides with the formation of glycerol and FFA. This effect is achieved by stimulation of cAMP and activation of hormone sensitive lipase. Strengthening of lipolysis is accompanied by an increase in blood FFA, their inclusion in the liver and the formation of keto acids. Glucagon stimulates glycogenolysis in the cardiac muscle, which increases cardiac output, increases arterioles and reduces total peripheral resistance, reduces platelet aggregation, gastric secretion, pancreosimin and pancreatic enzymes. The formation of insulin, growth hormone, calcitonin, catecholamines, secretion of fluid and electrolytes with urine under the influence of glucagon increase. Its basal level in the blood plasma is 50-70 pg / ml. After taking protein foods, during fasting, with chronic liver disease, chronic kidney failure, glucagonome, the glucagon content increases.

Somatostatin is a tetradecapeptide with a molecular weight of 1600 daltons, consisting of 13 amino acid residues with one disulfide bridge. Somatostatin was first detected in the anterior hypothalamus, and then in the nerve endings, synaptic vesicles, pancreas, gastrointestinal tract, thyroid gland, retina. The greatest amount of the hormone is formed in the anterior hypothalamus and D-cells of the pancreas. The biological role of somatostatin is to inhibit the secretion of somatotropic hormone, ACTH, TSH, gastrin, glucagon, insulin, renin, secretin, vasoactive gastric peptide (VGP), gastric juice, pancreatic enzymes and electrolytes. It lowers the absorption of xylose, the contractility of the gallbladder, the blood flow of internal organs (by 30-40%), intestinal motility, and also reduces the release of acetylcholine from nerve endings and electro-excitability of the nerves. The half-life of the parenterally introduced somatostatin is 1-2 min, which makes it possible to treat it as a hormone and a neurotransmitter. Many effects of somatostatin are mediated through its effect on the abovementioned organs and tissues. The mechanism of its action at the cellular level is still unclear. The content of somatostatin in the blood plasma of healthy individuals is 10-25 pg / l and increases in patients with type 1 diabetes, acromegaly and with D-cell pancreatic tumor (somatostatinoma).

The role of insulin, glucagon and somatostatin in homeostasis. In the energy balance of the body, the main role is played by insulin and glucagon, which support it at a certain level under various conditions of the body. During fasting, the level of insulin in the blood drops, and glucagon - increases, especially on the 3-5th day of fasting (about 3-5 times). Increased secretion of glucagon causes an increased disintegration of protein in the muscles and increases the process of gluconeogenesis, which contributes to the replenishment of glycogen in the liver. Thus, the constant level of glucose in the blood, necessary for the functioning of the brain, red blood cells, the medulla of the kidneys, is maintained through the enhancement of gluconeogenesis, glycogenolysis, suppression of glucose utilization by other tissues under the influence of increased glucagon secretion and reduced glucose intake by insulin-dependent tissues as a result of insulin production decline. During the day, the brain tissue absorbs from 100 to 150 g of glucose. Hyperproduction of glucagon stimulates lipolysis, which increases blood levels of FFA, which are used by the heart and other muscles, liver, kidneys as energy material. With prolonged starvation, keto acids formed in the liver become a source of energy. With natural fasting (during the night) or with long breaks in food intake (6-12 hours), energy needs of insulin-dependent body tissues are maintained due to fatty acids formed during lipolysis.

After eating (carbohydrate), a rapid increase in insulin levels and a decrease in glucagon in the blood are observed. The first causes the acceleration of glycogen synthesis and the utilization of glucose by insulin-dependent tissues. Protein food (for example, 200 g of meat) stimulates a sharp rise in the concentration of glucagon in the blood (by 50-100%) and insignificant - insulin, which enhances gluconeogenesis and increases glucose production by the liver.

[1], [2], [3], [4], [5], [6]