بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم ﴿و ما أوتيتم من العلم إلا قليلا﴾ صدق الله العظيم الاسراء اية 58

2. Regulation of Blood Glucose By Dr. Abdel Aziz M. Hussein Lecturer of Physiology Member of American Society of Physiology

3. Blood Glucose • The normal blood glucose level ranges ( ) 80-120 mg %. • The total amount of glucose in circulating blood is about 3.3 to 7gm • 5 grams of glucose is about equivalent to a commercial sugar packet (as provided in many restaurants with coffee or tea). • Failure to maintain blood glucose in the normal range leads to conditions of persistently high (hyperglycemia) or low (hypoglycemia) blood sugar.

4. Regulation of Blood Glucose Normal Blood glucose is regulated by 2 mechanisms:

5. A) Tissue Regulation

6. Liver • Liver maintains normal blood glucose level (glucose buffer function) by; • Glycogenesis (breakdown of glycogen into glucose) • Glycogenolysis (formation of glycogen from glucose) • Gluconeogenesis (formation of glucose from non carbohydrates fats and proteins)

7. Hormonal Regulation

8. B) Pancreatic Hormones

9. Pancreatic Hormones • Endocrine cells of the pancreas are present in groups called ‘islets of Langerhan’s’ • Are more numerous in the tail than in the body • Islets are 1-2% of its pancreatic weight

10. Pancreatic Hormones

12. Insulin Chemistry : • Insulin is secreted from beta cells of islets of Langerhans • Insulin is one of the most important peptide hormones. • It consists of 2 straight chains linked by 2 disulfide bridges. • A chain→ contains 21 amino acids and an intra-chain disulfide ring. • B chain→ contains 30 amino acids.

13. Insulin Mechanism of action: • Insulin acts on insulin receptor (2 subunits, alpha and beta subunits). • It is a tyrosine kinase i.e. functions as an enzyme that transfers phosphate groups from ATP to tyrosine residues on intracellular target proteins. • Binding of insulin to the alpha subunits causes the beta subunits to phosphorylate themselves (autophosphorylation), thus activating the catalytic activity of the receptor. • The activated receptor then phosphorylates a number of intracellular proteins called insulin-receptor substrates (IRS1-4).  • These substrates are coupled to several additional protein kinase signal systems

15. Physiological actions of Insulin

16. CHO and fat metabolism Insulin tends to lower blood glucose level i.e. hypoglycemic hormone, by: • Increase glucose uptake by the tissues (liver, ms, and fat tissues) by insertion of GLUT4 into cell membrane • Stimulate glycogenesis in Liver and SK. Ms • Inhibition of glycogenolysis • Inhibition of gluconeogenesis • Stimulate lipogenesis in adipose tissue N.B. • Insulin stimulate glucose entry in all tissues except brain cells, RBCs, intestinal cells and renal tubule cells

18. Insulin Action in Muscle and Fat CellsMobilization of GLUT4 to the Cell Surface Plasma membrane Insulin receptor Intracellular signaling cascades Intracellular GLUT4 vesicles Insulin GLUT4 vesicle mobilization to plasma membrane GLUT4 vesicle integration into plasma membrane Glucose entry into cell via GLUT4 vesicle Glucose GLUT4=glucose transporter 4

19. Protein and Mineral Metabolism Insulin is powerful anabolic hormone and stimulate tissue growth by : 1. Stimulates the uptake of certain amino acids by Sk. Ms 2. Stimulates the rate of protein synthesis (enhance activity of ribosomes) 3. Anticatabolic effects i.e. inhibits proteolysis. 4. Insulin increases cellular uptake of potassium, phosphate and magnesium

20. Regulation of Insulin Secretion

21. Stimuli of Insulin Secretion 1. Blood glucose: • Virtually, no insulin is secreted below a plasma glucose level of 50 mg%. • A half maximum insulin secretory response occurs at a plasma glucose level of about 150 mg% • A maximum response at 300 to 500 mg%. 2. GIT hormones: • Gastric inhibitory polypeptide (GIP): • The most important of insulinogogue i.e. stimulate insulin secretion b. High concentrations gastrin, secretin, cholecystokinin, pancreatic glucagons and enteroglucagon stimulate insulin secretion 3. ↑ Blood free fatty acids, ketoacids and triglycerides have little effect 4. ↑ blood amino acids e.g. arginine, leucine, lysine and alanine

22. Stimuli of Insulin Secretion 5. Other hormones e.g. Glucagon, GH, cortisol 6. Parasympathetic(Ach) andBeta adrenergic stimulation. 7. Obesity 8. Sulfonylurea drugs

23. Inhibitors of Insulin Secretion • Fasting • Exercise • Somatostatin • -Adrenergic stimuli • Prostaglandins • Drugs e.g. Diazoxide and Phenytoin

24. Glucagon Chemistry : • Polypeptide hormone (29 amino acid) • Secreted by  cells of the pancreatic islets. Functions : 1. On CHO metabolism: • It increases blood glucose i.e. hyperglycemic hormone by: • It stimulate glycogenolysis • It stimulates gluconeogenesis 2. It stimulates lipolysis 4. It inhibits renal tubular Na reabsorption. 5. It stimulates cardiac contractility

25. Glucagon Functions : 2. Glucagon activates adipose tissue lipase→ lipolysis→ delivery of free fatty acids from adipose tissue to the liver and ketogenesis. 3. It decreases hepatic cholesterol synthesis. 4.Natriuresis, by inhibition of renal tubular Na reabsorption. 5. Activation of myocardial adenyl cyclase, causing a moderate increase of cardiac output. 6. May act as a local CNS hormone for the regulation of appetite.

27. Other hormones regulating Blood Glucose

28. Other hormones regulating blood glucose 1. Adrenaline: glycogenolytic acting on both liver and muscles. 2. Glucocorticoids: Stimulate gluconeogenesis and depress glucose uptake by the tissues. 3. Growth hormone: Stimulates the release of glucagon hormone and also inhibits glucose uptake by tissues. 4. Thyroxin:It increases glucose absorption from the intestine, glycogenolysis and glucose uptake by cells. The net result is a rise in blood glucose level.

29. Summary of Regulation of Blood Glucose

30. Summary of Regulation of Blood Glucose

31. Importance of Regulation of Blood Glucose

32. Importance of blood glucose regulation • Maintenance of blood glucose constant is important because; • glucose is the only nutrient used by the brain, retina and germinal epithelium of the gonads • Too high blood glucose level produce many harmful effects such as; • Glucose can exert a large amount of osmotic pressure in the ECF that leads to cellular dehydration • Loss of glucose in urine • Osmotic diuresis by the kidneys • Long-term increases in blood glucose may cause damage to many tissues especially to blood vessels→ ↑es risk for heart attacks and cerebral strokes.

33. THANKS