Downloaded 383 times
More Related Content
Similar to Glucagon and its metabolic effects
Glucagon and its metabolic effects
- 1. GLUCAGON and ITSMETABOLIC EFFECTS BY: Khuram Aziz M.Phill Biochemistry Scientist by IBC Life Sciences Member of Pakistan Young Scientist Association
- 2. OUTLINE • Glucose homeostasis • Sources of glucose • Glucagon • Metabolic effects • Stimulation of Glucagon • Physiological actions • Regulation • Mechanism of glucagon
- 3. Glucose Equilibrium –A Wonder !! • Normal Blood Glucose – Fasting state : 60 to 100 mg% – Postprandial : 100 to 140 mg % Let us grasp some blood glucose in such a • What keeps the of the fascinating answers !! narrow range? • Why are we not becoming hypoglycemic when we fast? • Why is our blood sugar not shooting up to very high levels after a rich meal ? • What are the regulatory and counter regulatory hormones ? 3
- 4. Hormonal Regulation ofMetabolism • Balance between anabolism and catabolism depends on levels of insulin, glucagon, GH, thyroxine, and others 19-35
- 5. Insulin and GlucagonSecretion • Normal fasting glucose level is 60– 100 mg/dl – Insulin and glucagon normally prevent levels from rising above 170mg/dl after meals or falling below 50mg/dl between meals 19-40
- 6. Glucose Homeostasis Lower Blood Glucose Between meals -cells release -cells release Glucagon insulin stimulate glycogen stimulate glucose breakdown and uptake by gluconeogenesis peripheral tissues Higher Blood Glucose Food 6
- 7. Homeostasis of Glucose Counter Regulation Mechanisms • A steady maintenance of blood glucose with in a narrow range • Fasting state and fed states – their effects on BG • Rate of glucose appearance Ra • Rate of disappearance Rd must be in balance • Blood Glucose (BG) = Ra - Rd • Control systems – Glucose Receptors, GLUT 1-14 – Controlling Hormones, Insulin, Glucagon, Cortisol, Epinephrine etc., – Insulin Signaling sequences, Glucagon signaling – Effector Cells – Muscles, Liver, Brain, Heart and Adipose tissue – Feedback loops • Negative feedback • Positive feedback 7
- 8. Sources of Glucosein to blood • Glucose is derived from 3 sources • Intestinal absorption of dietary carbohydrates • Glycogen breakdown in liver and in the kidney. • Only liver and kidney have glucose-6-phosphatase. • Liver stores 25-138 grams of glycogen, a 3 to 8 hour supply. • Gluconeogenesis, the formation of glucose from precursors • These include lactate and pyruvate, amino acids (alanine and glutamine), and to a lesser degree, from glycerol 8
- 9. Fasting State • Short fast – Utilizes free glucose (15-20%) – Break down of glycogen (75%) • Overnight fast – Glycogen breakdown (75%) – Gluconeogenesis (25%) • Prolonged fast – Only 10 grams or less of liver glycogen remains. – Gluconeogenesis becomes sole source of glucose – Muscle protein is degraded for amino acids. – Lipolysis generates ketones for additional fuel. 9
- 10. Counter Regulatory Hormones •Glucagon We will discuss in detail • GLP-1 (Glucagon Like Peptide -1) – The most potent known insulin Secretagogue – It is made in the intestine by alternative processing of the same precursor • Intracellular actions 10
- 11. Responses to decreasingGlucose levels Response Glycemic Physiological Role in counter theshhold effects regulation ↓ Insulin 80 - 85 mg% ↑ Ra (↓ Rd) Primary First Defense ↑ Glucagon 65 - 70 mg% ↑ Ra Primary Second Defense ↑ Epinephrine 65 - 70 mg% ↑ Ra ↓ Rd Critical Third Defense ↑ Cortisol, GH 65 - 70 mg% ↑ R a ↓ Rd Not Critical ↑ Food ingestion 50 - 55 mg% ↑ Exogenous < 50mg% no Glucose cognitive change 11
- 12. Glucagon • It isa peptide hormone. • Consists of a single chain of 29 amino acids. • Secreted by alpha cells of pancreatic islets of langerhans. • Its main action is on the liver. • It tends to increase the blood glucose level. • Known as hyperglycemic hormone.
- 13. Glucagon Secretion Stimulation of Glucagon secretion – Blood glucose < 70 mg/dL – High levels of circulating amino acids – Especially arginine and alanine – Sympathetic and parasympathetic stimulation – Catecholamines – Cholecystokinin, Gastrin – Glucocorticoids 13
- 14. Role of Glucagon • Metabolic Effects of Glucagon – Increases hepatic glycogenolysis – Increases gluconeogenesis – Increases amino acid transport – Increases fatty acid metabolism (ketogenesis) 14
- 15. Metabolic Effects ofGlucagon 15
- 16. Role of Glucagon • Metabolic Effects of Glucagon Clinical Pearl – Increases hepatic glycogenolysis 1. Glucagon is the treatment for hypoglycemia – Increases gluconeogenesis 2. Glucagon Kit – 1 mg s/c or IM or IV injection – – Increases amino acid transport 3. In 2 to 3 minutes recovery – Increases fatty acid metabolism (ketogenesis) 16
- 17. Physiological actions Glucagon On glucose On fats On insulin Increases Stimulates Decreases Blood glucose Insulin lipogenesis level secretion
- 18. Physiological actions Glucagon increases Blood glucose level Inhibiting Increases Glycogenolysis glycogen liver synthesis gluconeogenesis Increases Inhibits stimulate hepatic glycogen phosphorylase Production of synthase glucose
- 19. Physiological actions Glucagon Increase Decreases Increases Hepatic lipogenesis lipolysis utilization of fats stimulates Ketogenesis Inhibits Hormone Increase Acetyl CoA Sensitive Formation of carboxylase Lipase in ketones liver Increase Free fatty acid
- 20. Physiological actions High levels Of glucagon Increases Inhibits Increases blood flow in Increases bile Strength of some tissues Gastric acid secretion The heart secretion e.g the kidneys
- 21. Cell ATP sensitive K+ channel Voltage dependent Ca+ channel ATP Metabolism Glucokinase GLUCOSE INSULIN
- 22. Somatostatin inhibits glucagonand insulin secretion • somatostatin secretion is increased by the following;. 1-increased blood glucose 2-increased amino acids 3-increased fatty acids 4- increased concentrations of several of the gastrointestinal hormones released from the upper gastrointestinal tract in response to food uptake • In turn somatostatin has multiple inhibitory effects as follow: 1-acts locally within the islets of langerhans themselves to depress the secretion of both insulin and glucagon 2-decreases both secretion and absorption in the gastrointestinal tract 3-decrease the motility of the stomach ,duodenum, and gallbladder
- 23. Somatostatin Somatostatin -From delta cells -Inhibitory hormone Increase blood Increased amino glucose acids Increased fatty Upper acids GI-hormones Inhibts Decreases the Decreases both secretion Motility of stomach Secretion & Of insulin & Duodenum absorption in glucaon Gall bladder GIT
- 24. Regulation of glucagonsecretion - Increased blood glucose inhibits glucagon secretion : - increase blood amino acids stimulate glucagon secretion : High concentrations of amino acids as occur in the blood after protein meals stimulate the secretion of glucagon .this is the same effect that amino acids have in stimulating insulin secretion. Thus in this instance the glucagon and insulin responses are not opposite. - exercise stimulates glucagon secretion.
- 25. -exercise stimulates glucagonsecretion : In exhaustive exercise, the blood concentration of glucagon often increases fourfold to fivefold. A beneficial effect of the glucagon is that to prevents a decrease in blood glucose One of the factors that might increase glucagon secretion in exercise is increased circulating amino acids .other factors such as beta –adrenergic stimulation of the islets of langerhans ,may also play a role .
- 26. Regulation of bloodglucose Regulation of Blood glucose Severe Prolonged Hyperglycemia Hypoglycemia hypoglycemia hypoglycemia Release Release of Release of Catecholamine of GH insulin glucagon release & cortisol Glycogenesis Release of Glycogenolysis Glucose glucose Gluconeogenesis storage By the From fat Gluconeogenesis In liver liver Decreased Increased blood blood Glucose level Glucose level
- 28. GlucagonMechanism of action Binds to receptors On hepatocytes Stimulation Of adenyl cyclase ATP cAMP Activates protein kinases Desired action
- 29. Please note thatdue to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer. 17-29
- 30. cAMP and activationof PKA Glucagon or epinephrine Liver cell ATP inactive active cAMP adenylyl cyclase p inactive active cAMP inactive active glycogen inactive active phosphorylase p phosphorylase protein kinase kinase A glycogen glucose-1-phosphate amplification cascade
- 31. THANKS BEST OF LUCK