In this article we will discuss about the Chemistry and Functions of Glucagon.
Chemistry of Glucagon:
1. Glucagon is a polypeptide with a molecular weight of 3,485.
2. It consists of 29 amino acid having 15 different amino acids. The amino acids are arranged in a straight chain.
3. It contains no cystine, proline or isoleucine but contains sufficient amounts of methionine and tryptophan.
4. It can be crystallized in the absence of zinc or other metals.
5. A pro-glucagon precursor of about 9,000 Daltons is also identified.
6. It originates primarily in the alpha-cells of the pancreas, although a considerable amount comes from extra-hepatic alpha-cells in the stomach and other portions of the gastrointestinal tract.
7. A glucagon-like immunoreactive factor (GLI) is also identified in gastric and duodenal mucosa but less active than pancreatic glucagon.
Factors influencing secretions of glucagon:
1. Low blood glucose increases secretion of pancreatic glucagon.
2. Most amino acids, particularly arginine, cause a rapid secretion of glucagon from the pancreas.
3. Fatty acids inhibit glucagon release.
4. Exercise stimulates the secretion of glucagon.
5. During mixed meals, both insulin and glucagon are secreted, but the carbohydrate meal causes insulin release. High protein meal favours glucagon secretion.
6. In stress, insulin secretion is inhibited but glucagon secretion is stimulated.
Functions of Glucagon:
1. Glucagon is sensitive to the adenylate cyclase receptor sites in the liver and increases cAMP level. cAMP activates the enzyme protein kinase which further activates phosphorylase. Phosphorylase causes glycogenolysis making available of glucose in blood. cAMP suppresses glycogen synthetase. Thus, glucagon increases glycogen breakdown and inhibits synthesis of glycogen.
2. Glucagon can also activate various phospho-enzymes by activating protein kinase and inhibit de-phospho-enzymes. Thus, glucagon can directly stimulate gluconeogenesis by activation of pyruvate carboxylase and fructose-1, 6-di-phosphatase.
3. It also inhibits glucose oxidation by inhibiting pyruvate kinase and pyruvate dehydrogenase.
4. Elevated glucagon concentration also increases ketogenesis.
5. It increases potassium release from the liver.
6. In adipose tissue as well as in liver, it increases the breakdown of lipids to fatty acids and glycerol.
7. Crystalline glucagon polypeptide is used for the treatment of hypoglycemic persons. Glucagon is also used as a diagnostic test for glycogen storage disease.
Normal level of glucagon (fasting) in serum: 20-100 Pg/ml.