Glucagon is a hormone of the alpha cells of the islets of Langerhans in the pancreas. By chemical structure, glucagon is a peptide hormone.
The glucagon molecule consists of 29 amino acids and has a molecular weight of 3485 daltons. Glucagon was discovered in 1923 by Kimbell and Merlin.
The primary structure of the glucagon molecule is as follows: NH2-His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp- Phe-Val-Gln-Trp-Leu- Met-Asn-Thr-COOH
The mechanism of action of glucagon is due to its binding to specific glucagon receptors of liver cells. This leads to an increase in G-protein-mediated adenylate cyclase activity and an increase in cAMP production. The result is an increase in the catabolism of glycogen deposited in the liver (glycogenolysis). Glucagon for hepatocytes serves as an external signal about the need to release glucose into the blood due to the breakdown of glycogen (glycogenolysis) or the synthesis of glucose from other substances – gluconeogenesis. The hormone binds to a receptor on the plasma membrane and activates adenylate cyclase mediated by the G-protein, which catalyzes the formation of cAMP from ATP. This is followed by a cascade of reactions leading to the activation of glycogen phosphorylase and inhibition of glycogen synthase in the liver. This mechanism leads to the release of glucose-1-phosphate from glycogen, which is converted into glucose-6-phosphate. Then, under the influence of glucose-6-phosphatase, free glucose is formed, which can leave the cell into the blood. Thus, glucagon in the liver, by stimulating the breakdown of glycogen, contributes to the maintenance of glucose in the blood at a constant level. Glucagon also activates gluconeogenesis, lipolysis, and ketogenesis in the liver.
Glucagon has practically no effect on skeletal muscle glycogen, apparently due to the almost complete absence of glucagon receptors in them. Glucagon causes an increase in insulin secretion from healthy β-cells of the pancreas and inhibition of insulinase activity. This appears to be one of the physiological mechanisms of counteracting glucagon-induced hyperglycemia.
Glucagon has a strong inotropic and chronotropic effect on the myocardium due to an increase in the formation of cAMP (that is, it has an effect similar to the action of β-adrenergic receptor agonists, but without the involvement of β-adrenergic systems in the implementation of this effect). The result is an increase in blood pressure, an increase in heart rate and strength.
In high concentrations, glucagon causes a strong antispasmodic effect, relaxation of the smooth muscles of internal organs, especially the intestines, not mediated by adenylate cyclase.
Glucagon is involved in the fight-or-flight reactions, increasing the availability of energy substrates (in particular, glucose, free fatty acids, keto acids) for skeletal muscles and increasing the blood supply to skeletal muscles by increasing the work of the heart. In addition, glucagon increases the secretion of catecholamines by the adrenal medulla and increases the sensitivity of tissues to catecholamines, which also favors the implementation of “fight or flight” reactions.
Below is a list of glucagon and its analogues: