The following points highlight the top three effects of glucagon. The effects are:- 1. Effects on Carbohydrate Metabolism 2. Effects on Lipid Metabolism 3. Effects on Ketogenesis.
1. Effects on Carbohydrate Metabolism:
The hyperglycemic effects of glucagon are exhibited in several ways:
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(a) It enhances hepatic gluconeogenesis from amino acids by stimulating the enzymes of gluconeogenic pathways like fructose 1, 6 bisphosphatase, PEP carboxykinase and pyruvate carboxylase.
(b) It also increases hepatic glycogenolysis by activating the important enzymes of that pathways like glycogen phosphorylase and glucose 6-phosphatase.
(c) Glucagon inhibits hepatic glycogenesis by inhibiting the rate-limiting enzyme, glycogen synthase of that pathway and also by repressing the first enzyme of that pathway, the glucokinase.
(d) It inactivates the pyruvate kinase and pyruvate dehydrogenase and thus, inhibits glucose utilisation by the hepatic cells.
2. Effects on Lipid Metabolism:
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(a) Lipolysis:
In adipose tissues glucagon stimulates lipolysis or lipid breakdown. Glucagon actually stimulates the triacylglycerol lipase activity in the adipocytes and, thus, lipolysis is enhanced, resulting in mobilisation of released fatty acids into blood. As a result β-oxidation and ketosis are augmented.
(b) Lipogenesis:
The hormone inhibits fatty acid synthesis. The rate limiting enzyme of lipogenesis is the acetyl CoA carboxylase which is inactivated by glucagon. Glucagon promotes lipolysis and fatty acid mobilisation as mentioned above and thus, it raises the cytoplasmic levels of long-chain acyl- CoA molecules in adipocytes and hepatocytes.
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This in turn, inhibits, the rate limiting enzyme acetyl CoA-carboxylase. Again, the hormone can activate a protein kinase which phosphorylates and, consequently, inactivates the rate-limiting acetyl CoA carboxylase of lipogenesis.
3. Effects on Ketogenesis:
Glucagon induces kitogenesis. Malonyl CoA, the product of the first committed step in lipogenesis is reduced by glucagon. This abolishes the inhibitory action of malonyl CoA on carnitine palmitoyltransferase I (CPT-I), the enzyme responsible for trans-esterification of fatty acyl CoA to fatty acyl carnitine.
Thus, allowing the fatty acids to enter the mitochondria to undergo β-oxidation to ketones. Glucagon also increases hepatic carnitine levels by an unknown mechanism. The combination of increased fatty acyl CoA and carnitine levels and activated CPT-I ensures brisk rates of ketogenesis.