PANCREAS The pancreas secretes tow important hormones insulin

PANCREAS The pancreas secretes tow important hormones, insulin and glucagon. Physiologic Anatomy Of The Pancreas The pancreas is composed of tow major of tissues:

PANCREAS n 1 -The acini which secrete digestive juices into the duodenum. n 2 -The islets of Langerhans, which secrete insulin and glucagons directly into the blood. It is formed of three types of cells, the alpha, beta and delta cells. n The beta cells secrete insulin, the alpha cells secrete glucagon, and the delta cells secrete somatostatin.

INSULIN n Insulin is a small protein molecule composed of two amino acid chains, connected to each other by disulfide linkages. When insulin is secreted into the blood , it circulates almost entirely in an unbound form

Functions of insulin a-Effect of insulin on carbohydrate metabolism: n 1 -Insulin facilitates the entry of glucose into the cells(muscles, adipose tissues and connective tissues. ) by an action on the cell membrane &increases its utilization. n The normal resting muscle membrane is almost impermeable to glucose except when the muscle fiber is stimulated by insulin. n

Functions of insulin -During periods of heavy exercise, exercising muscle fibers become highly permeable to glucose even in the absence of insulin because of the concentration process itself. -Few hours after a meal, the blood glucose concentration is high; also the pancreas is secreting large quantities of insulin which causes rapid transport of glucose into the muscle cells to be stored in the form of glycogen. n

Functions of insulin The brain cells are permeable to glucose without the intermediation of insulin except the satiety center. n 2 -Insulin facilitates glycogen synthesis in the liver by increasing the activity of enzyme required formation of glycogen. n 3 -Insulin inhibits gluconeogenesis by decreasing the quantities and activities of the liver enzymes required for gluconeogenesis. n

b-Effect of insulin on fat metabolism -Insulin increases the utilization of glucose which automatically decreases the utilization of fat , thus functioning as a fat sparer. n -Insulin also promotes fatty acid synthesis in the cells and adipose tissue. n -All aspects of fat metabolism are greatly enhanced in the absence of insulin. n

c-Effect of insulin on protein metabolism n -Insulin causes active transport of many of the a. a into the cells. n -Insulin has a direct effect on the ribosomes to increase the translation of m. RNA , thus forming new proteins. -Insulin also inhibits the catabolism of proteins. n -In the liver, insulin depresses the rate of gluconeogenesis. This conserves the amino acids in the protein stores of the body.

d-Effect of insulin on growth n Insulin has a synergetic effect with growth hormone. Each promotes cellular uptake of a different selection of amino acids, all of which are required for growth.

e-Effect of insulin on K+ n It causes K+ enter muscle cells. The reason is that insulin increases the activity of Na+ K+ATPase in the cell membrane more K+ is pumped into cell.

CONTROL OF INSULIN SECRETION 1 -Stimulation of insulin secretion by blood glucose: n At the normal fasting level of blood glucose of 80 -90 mg/dl , the rate of insulin secretion is minimal. If the blood glucose concentration is suddenly increased to a level 23 times normal, insulin secretion increases. n Glucose penetrate the beta cells directly and its rate of entrance is unaffected by insulin. When the level of glucose in the pancreas is increased insulin secretion increase. n

CONTROL OF INSULIN SECRETION n 2 -Amino n acids: They potentate the glucose stimulus for insulin secretion, e. g. arginin and lysine.

CONTROL OF INSULIN SECRETION n n n 3 -Depletion of K+ decreases insulin secretion. 4 -Gastrointestinal hormones: Gastrin, secretin, CCK&GIP may cause moderate increase in insulin secretion. 5 -Other hormones: Include glucagons, GH, cortisol , progesterone and estrogen. Prolonged secretion of any one of them in large quantities can occasionally lead to exhaustion of the beta cells of the islets of Langerhans and thereby cause diabetes.

CONTROL OF INSULIN SECRETION 6 -Autonomic nervous system: n The autonomic innervation of the pancreas is involved in the regulation of insulin secretion. Stimulation of the vagus nerve causes increased insulin secretion. Stimulation of the sympathetic nerves to the pancreas inhibits insulin secretion. The inhibition is produced by released nor epinephrine acting on alpha-2 adrenergic receptors. n

GLUCAGON Glucagon is a hyperglycemic hormone secreted by the alpha cells of the islets of Langerhans when the blood glucose concentration falls. It is a large polypeptide. n Actions of glucagons: n 1 -It rises blood glucose level because it stimulates adenyl cyclase in liver cells. n 2 -It increases breakdown of glycogen in liver but not in muscle(glycogenolysis). n

GLUCAGON n 3 -It increases gluconeogenisis from available a. a in the liver. n 4 -It increases ketone body formation due to its lipolytic effect. n 5 -It increase metabolic rate because it increase hepatic deamination of a. a. n 6 -It stimulates the secretion of GH, insulin and pancreatic somatostatin.

Regulation of glucagons secretion n 1 -Decrease in the blood glucose concentration increases glucagons secretion. n 2 -Increasing the blood glucose to hyperglycemic levels decrease plasma glucagons. n 3 -High concentrations of a. a after a protein meal stimulate the secretion of glucagons.

Regulation of glucagons secretion n 4 -In exercise the blood concentration of glucagons often increases to increase glucose production by the liver. n 5 -Secretion is increased by stimulation of the sympathetic nerves to the pancreas. n 6 -CCK and gastrin increases glucagons secretion but secretion inhibits it.

SOMATOSTATIN n It is secreted by the delta cells of the islets of Langerhans. Somatostatin is a polypeptide, it is the same chemical substance as growth hormone inhibitory hormone (GHIH)that is secreted in the hypothalamus. All factors related to the ingestion of food will stimulate somatostatin secretion. These include:

SOMATOSTATIN n n n 1 -↑ blood glucose. 2 -↑ A. A. 3 - ↑ F. A. 4 - ↑ concentrations of several of the GIT hormones in response to food intake. Somatostatin has multiple inhibitory effects as follows: 1 -It acts locally within the islets of Langerhans themselves to depress the secretion of both insulin and glucagons.

SOMATOSTATIN n 2 -It decreases the motility of the stomach, the duodenum and the gallbladder. n 3 - It decreases both secretion and absorption in the GIT. n Excess somatostatin due to the tumor causes hyperglycemia , dyspepsia and gall stone.

DIABETES MELLITUS n Diabetes mellitus (D. M) is caused by diminished rates of secretion of insulin by the beta cells of the islets of Langerhans. It is of 2 types, juvenile diabetes that begins in early life and maturity –onset diabetes which begins in later life and mainly in obese persons. n Manifestation of D. M: n Deficiency of insulin causes disturbances in CHO, fats, and protein metabolism.

DIABETES MELLITUS n 1 -Disturbance in CHO metabolism: -Polyuria n -Polydepsia n -Poly phagia. n -Dehydration, hypovolemia and hypotension. n

DIABETES MELLITUS n 2 -Disturbances in protein metabolism n -Protein synthesis stops so the rate of growth is decreased specially in diabetic children and asthenia in adults. n -Catabolism of proteins increases. n -Most of the excess AAs are either used directly for energy or for gluconeogenesis. n -

DIABETES MELLITUS n Degradation of the a. a increases urea excretion in the urine. n -Poor resistance to infection due to decrease of protein & sugar rich body fluids are good culture media for microorganisms.

DIABETES MELLITUS n n 3 -Disturbance in fat metabolism which leads to: -Hydrolysis of the stored TG resulting large quantities of FFAs & glycerol into the blood. -FFAs then becomes the main energy substrate used by essentially tissues of the body. -↑ FFAs in the blood causes rapid diffusion of FAs into the liver cells.

DIABETES MELLITUS - ↓ insulin & ↑FAs in the liver cells , → βoxidation of the FAs →releasing extreme amounts of acetyl-Co. A. →converted to acetoacetic acid→converted into acetyl. Co. A.

DIABETES MELLITUS -Some, of the acetoacetic acid , →Bhydroxybutyric acid and acetone, these tow substances are called ketone bodies, → ketosis. n The acetoacetic acid and the B-hydroxybutyric acid can cause severe acidosis and coma. n -The liver form TG , phospholipids and cholesterol , this leads to rapid development of atherosclerosis & fatty liver. n

HYPERINSULINISM n Increased insulin production results from an adenoma of an islet of Langerhans, Excess insulin causes the level of blood glucose to fall to low values which affects the especially the brain cells.

HYPERINSULINISM n When the blood glucose falls too low(2050 mg%)symptoms of hypoglycemic shock develop, characterized by progressive irritability that leads to fainting, convulsios &coma