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 hilum of the spleen. Its length is about 15 cm, weight is about 100 g. The pancreas has a head located in the arch of the duodenum, a body and a tail reaching the hilum of the spleen and lying retroperitoneally. The blood supply to the pancreas is carried out by the splenic and superior mesenteric artery. Venous blood enters the splenic and superior mesenteric veins. The pancreas is innervated by sympathetic and parasympathetic nerves, the terminal fibers of which contact the cell membrane of the islet cells.

The pancreas has exocrine and endocrine functions. The latter is performed by the islets of Langerhans, which make up about 1-3% of the gland's mass (from 1 to 1.5 million). The diameter of each is about 150 µm. One islet contains from 80 to 200 cells. There are several types of them, depending on their ability to secrete polypeptide hormones. A-cells produce glucagon, B-cells produce insulin, and D-cells produce somatostatin. A number of islet cells have also been discovered, which are supposed to produce vasoactive interstitial polypeptide (VIP), gastrointestinal peptide (GIP), and pancreatic polypeptide. B-cells are localized in the center of the islet, and the rest are located on its periphery. The bulk of the mass - 60% of the cells - are B-cells, 25% - A-cells, 10% - D-cells, and the rest - 5% of the mass.

Insulin is formed in B-cells from its precursor, proinsulin, which is synthesized on the ribosomes of the rough endoplasmic reticulum. Proinsulin consists of 3 peptide chains (A, B, and C). The A- and B-chains are connected by disulfide bridges, and the C-peptide links the A- and B-chains. The molecular weight of proinsulin is 9,000 daltons. Synthesized proinsulin enters the Golgi apparatus, where it is broken down by proteolytic enzymes 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 attached to 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 (lamellar complex), insulin, C-peptide and partially proinsulin enter vesicles, where the former binds to zinc and is deposited in a crystalline state. Under the influence of various stimuli, vesicles move to the cytoplasmic membrane and release insulin in a dissolved form into the precapillary space by emyocytosis.

The most powerful stimulator of its secretion is glucose, which interacts with receptors of the cytoplasmic membrane. The insulin response to its effect is two-phase: the first phase - fast - corresponds to the release of reserves of synthesized insulin (1st pool), the second - slow - characterizes the speed of its synthesis (2nd pool). The signal from the cytoplasmic enzyme - adenylate cyclase - is transmitted to the cAMP system, mobilizing calcium from the mitochondria, which participates in the release of insulin. In addition to glucose, amino acids (arginine, leucine), glucagon, gastrin, secretin, pancreozymin, gastric inhibitory polypeptide, neurotensin, bombesin, sulfanilamide drugs, beta-adrenergic stimulants, glucocorticoids, STH, ACTH have a stimulating effect on the release and secretion of insulin. Hypoglycemia, somatostatin, nicotinic acid, diazoxide, alpha-adrenergic stimulation, phenytoin, and phenothiazines suppress the secretion and release of insulin.

Insulin in the blood is free (immunoreactive insulin, IRI) and bound to plasma proteins. Insulin degradation 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 are also subject to degradation in the liver, but much more slowly.

Insulin has multiple effects on insulin-dependent tissues (liver, muscles, adipose tissue). It has no direct effect on renal and nervous tissue, the lens, and erythrocytes. Insulin is an anabolic hormone that enhances the synthesis of carbohydrates, proteins, nucleic acids, and fat. Its effect on carbohydrate metabolism is expressed in increased glucose transport into 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 stimulation of amino acid transport through the cytoplasmic membrane of cells, protein synthesis, and inhibition of its breakdown. Its participation in fat metabolism is characterized by the inclusion of fatty acids in adipose tissue triglycerides, 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 cellular cytoplasmic membrane. After binding to them, the signal is transmitted through an enzyme built into the cell membrane - adenylate cyclase - to the cAMP system, which, with the participation of calcium and magnesium, regulates protein synthesis and glucose utilization.

The basal concentration of insulin, determined radioimmunologically, is 15-20 μU/ml in healthy individuals. After an oral glucose load (100 g), its level increases 5-10 times compared to the initial level after 1 hour. The rate of insulin secretion on an empty stomach is 0.5-1 U/h, and after a meal it increases to 2.5-5 U/h. Insulin secretion is increased by parasympathetic stimulation and decreased by sympathetic stimulation.

Glucagon is a single-chain polypeptide with a molecular weight of 3485 daltons. It consists of 29 amino acid residues. It is broken down in the body by proteolytic enzymes. Glucagon secretion is regulated by glucose, amino acids, gastrointestinal hormones, and the sympathetic nervous system. It is enhanced by hypoglycemia, arginine, gastrointestinal hormones, especially pancreozymin, factors stimulating the sympathetic nervous system (physical activity, etc.), and a decrease in the blood levels of free fatty acids.

Glucagon production is inhibited by somatostatin, hyperglycemia, and elevated levels of free fatty acids in the blood. The glucagon content in the blood increases with decompensated diabetes mellitus and glucagonoma. The half-life of glucagon is 10 minutes. It is inactivated primarily in the liver and kidneys by splitting into inactive fragments under the influence of carboxypeptidase, trypsin, chymotrypsin, etc. enzymes.

The main mechanism of glucagon action is characterized by an increase in glucose production by the liver by stimulating its breakdown and activating gluconeogenesis. Glucagon binds to hepatocyte membrane receptors and activates the enzyme adenylate cyclase, which stimulates the formation of cAMP. This leads to the accumulation of the active form of phosphorylase, which participates in the process of gluconeogenesis. 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 adipose tissue. By binding to adipocyte receptors, glucagon promotes the hydrolysis of triglycerides with the formation of glycerol and free fatty acids. This effect is achieved by stimulating cAMP and activating hormone-sensitive lipase. Increased lipolysis is accompanied by an increase in free fatty acids in the blood, their inclusion in the liver and the formation of keto acids. Glucagon stimulates glycogenolysis in the cardiac muscle, which increases cardiac output, dilates arterioles and reduces total peripheral resistance, reduces platelet aggregation, secretion of gastrin, pancreozymin and pancreatic enzymes. The formation of insulin, somatotropic hormone, calcitonin, catecholamines, and the excretion of fluid and electrolytes in the urine increase under the influence of glucagon. Its basal level in blood plasma is 50-70 pg/ml. After taking protein foods, during fasting, in chronic liver disease, chronic renal failure, and glucagonoma, 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 discovered in the anterior hypothalamus, and then in nerve endings, synaptic vesicles, pancreas, gastrointestinal tract, thyroid gland, and retina. The largest amount of the hormone is formed in the anterior hypothalamus and D-cells of the pancreas. The biological role of somatostatin is to suppress the secretion of somatotropic hormone, ACTH, TSH, gastrin, glucagon, insulin, renin, secretin, vasoactive gastric peptide (VGP), gastric juice, pancreatic enzymes, and electrolytes. It reduces xylose absorption, gallbladder contractility, blood flow in internal organs (by 30-40%), intestinal peristalsis, and also reduces the release of acetylcholine from nerve endings and electrical excitability of nerves. The half-life of parenterally administered somatostatin is 1-2 minutes, which allows us to consider it as a hormone and neurotransmitter. Many effects of somatostatin are mediated through its influence on the above-mentioned organs and tissues. The mechanism of its action at the cellular level is still unclear. The somatostatin content in the blood plasma of healthy individuals is 10-25 pg/l and increases in patients with type I diabetes mellitus, acromegaly, and D-cell tumor of the pancreas (somatostatinoma).

The role of insulin, glucagon and somatostatin in homeostasis. Insulin and glucagon play the main role in the body's energy balance, maintaining it at a certain level in various states of the body. During fasting, the level of insulin in the blood decreases, and glucagon increases, especially on the 3rd-5th day of fasting (approximately 3-5 times). Increased secretion of glucagon causes increased protein breakdown in muscles and increases the process of gluconeogenesis, which helps replenish glycogen reserves in the liver. Thus, a constant level of glucose in the blood, necessary for the functioning of the brain, erythrocytes, and the renal medulla, is maintained by enhancing gluconeogenesis, glycogenolysis, suppressing glucose utilization by other tissues under the influence of increased secretion of glucagon and reducing glucose consumption by insulin-dependent tissues as a result of decreased insulin production. During the day, brain tissue absorbs from 100 to 150 g of glucose. Hyperproduction of glucagon stimulates lipolysis, which increases the level of free fatty acids in the blood, which are used by the heart and other muscles, liver, and kidneys as energy material. During prolonged fasting, keto acids formed in the liver also become a source of energy. During natural fasting (overnight) or during long breaks in food intake (6-12 hours), the energy needs of insulin-dependent tissues of the body are maintained by fatty acids formed during lipolysis.

After eating (carbohydrates), a rapid increase in insulin levels and a decrease in glucagon levels in the blood are observed. The former causes an acceleration of glycogen synthesis and the utilization of glucose by insulin-dependent tissues. Protein foods (for example, 200 g of meat) stimulate a sharp increase in the concentration of glucagon in the blood (by 50-100%) and an insignificant increase in insulin, which contributes to increased gluconeogenesis and an increase in glucose production by the liver.

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