Glucagon Physiology

Overview
  • Glucagon is a hormone secreted during times of low nutrient intake and modifies hepatic metabolism to boost blood glucose concentration. As such, glucagon is an important factor involved in blood glucose regulation.
Biochemistry
  • Glucagon is a peptide hormone synthesized by the alpha cells of the endocrine pancreas. Like insulin, glucagon is synthesized from a precursor, preproglucagon, as is any other cellular protein and is stored in secretory granules until its regulated release.
Regulation
  • The primary physiological variable which regulates glucagon synthesis and release is blood glucose concentration. In contrast to insulin, glucagon is released when blood glucose concentrations are low.
Molecular Action
  • The molecular effects of glucagon are mediated by its specific binding to glucagon receptor, a GPCR, primarily present on hepatocytes. Binding of glucagon to glucagon receptor results in the activation of Gs and subsequently adenylyl cyclase, resulting in increases in intracellular cAMP levels that cause activation of a wide variety of protein kinases. Activation of these kinases ultimately coordinates far-reaching changes in hepatocyte biochemistry which mediate glucagon's physiological effects.
Physiological Action
  • The primary physiological actions of glucagon are focused on the liver and it induces hepatic release of glucose to boost blood glucose concentration. When the liver possesses glycogen, glucagon inhibits hepatic glycogenesis and promotes glycogenolysis. Once hepatic glycogen stores are exhausted, glucagon serves to activate hepatic gluconeogenesis. These features of glucagon make it an important component in processes of blood glucose regulation. A number of other metabolic effects of glucagon have been described in animals, especially in lipid metabolism; however, these were achieved by supra-physiological levels of the hormone and likely are not of physiological significance.