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Hormonal regulation of carbohydrate metabolism

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1 Hormonal regulation of carbohydrate metabolism
Liver, extrahepatic tissues and hormones play a major role In the regulation of blood glucose. Hormonal regulation of glucose in fed state: Increased level of circulating glucose releases insulin and this hormone reduces the blood glucose level in many ways Dr S Nayak

2 Glucokinase is important in regulating blood glucose after meal.
It stimulates the GLUT-4 transporter to increase the active transport of glucose across membranes of muscle and adipose tissue. Glucose is rapidly taken up into liver via GLUT-2 transporter In the liver insulin increases the of glycolysis by inducing the glycolytic enzymes like glucokinase , phosphofructokinase and pyruvate kinase. Glucokinase is important in regulating blood glucose after meal. Dr S Nayak

3 In the liver and muscle insulin stimulates glycogenesis by stimulating glycogen synthase [by reducing the elevated cAMP levels] and thereby leading to suppression of glycogenolysis Insulin inhibits gluconeogenesis by suppressing the action of key enzymes of gluconeogenesis [ puyruvate carboxylase, PEPCK, fructose 1,6-bisphosphatase and glucose 6-phosphatase] In adipose tissue, glucose is converted to the glycerol 3-phosphate, needed for the formation of triacylglycerol and inhibits the lipolysis by inhibiting hormone sensitive lipase. Insulin increases protein synthesis and decreases protein catabolism, thereby decreasing releasing amino acids for gluconeogenesis Dr S Nayak

4 Hormonal regulation of fat metabolism
Insulin inhibit the activity of hormone sensitive lipase and reduces the release of free fatty acids and glycerol from the adipose tissue, this results in fall in the circulating plasma free fatty acids Insulin enhances: Triacylglycerol synthesis Lipogenesis both in liver and adipose tissue by stimulating pyruvate dehydrogenase, acetyl CoA carboxylase and glycerol phosphate acyltransferase Dr S Nayak

5 Regulation of carbohydrate metabolism in fasting state Glucagon
In the liver, it stimulates glycogenolysis by activating glycogen phosphorylase and inhibits glycogen synthase. It exerts its action on metabolic processes through the generation of cAMP Stimulates gluconeogenesis Enhances gluconeogenesis from amino acids and lactate Alanine is the predominant amino acid released from muscle to liver by glucose alanine cycle Epinephrine Favors glycogenolysis in liver and muscle through cAMP dependent activation of adenylyl cyclase which converts ATP to cAMP [stimulates phosphorylase] Dr S Nayak

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7 Protein catabolism to provide amino acids for gluconeogenesis
Glucocorticoids Increases: Gluconeogenesis, Protein catabolism to provide amino acids for gluconeogenesis Acitivity of aminotransferase [to convert pyruavte to alanine] Hepatic uptake of amino acids Activity of key enzymes of gluconeogenesis Glucocorticoids inhibit the utilization of glucose in extrahepatic tissues Anterior pituitary hormones Growth hormone and ACTH antagonize the action of insulin by elevating the blood glucose level GH decreases glucose uptake in the muscle and ACTH decreases glucose utilization by the tissue Thyroxine Accelerates liver glycogenolysis and increase the rate of absorption of hexoses from the intestine Dr S Nayak

8 Hormonal regulation of fat metabolism Normally Insulin
Inhibit the activity of hormone sensitive lipase and reduces the release of free fatty acids and glycerol from the adipose tissue Enhances Triacylglycerol synthesis, lipogenesis both in liver and adipose tissue by stimulating pyruvate dehydrogenase, acetyl CoA carboxylase and glycerol phosphate acyltransferase Starvation associated with decreased activity of insulin and increased activity of glucagon, therefore the hyperglycemic hormones antagonizes the action of insulin Norepinephrine, glucagon, ACTH,GH and vasopressin accelerate the release of free fatty acids from adipose tissue and raise the plasma free fatty acid concentration by increasing the lipolysis of the TG Dr S Nayak

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10 Hormonal regulation of cholesterol metabolism
cAMP, by stimulating cAMP dependent protein kinase , activates hormone sensitive lipase Glucagon, epinephrine & norepinephrine inactivate the enzyme by cAMP dependent phosphorylation and inhibit the fatty acid synthesis Hormonal regulation of cholesterol metabolism The HMG CoA reductase is the regulatory enzyme of cholesterol synthesis Insulin and thyroid hormones Increase HMG CoA reductase activity through dephosphorylation of the enzyme [active] Glucagon and glucocorticoids decrease HMG-CoA reductase activity through cAMP dependent phosphorylation [inactive]. Dr S Nayak

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