Revisiting the Pharmacological Value of Glucagon: An Editorial for the Special Issue The Biology and Pharmacology of Glucagon

摘要

In 1921, a Canadian research team led by Frederick Banting and John Macleod succeeded in the isolation of insulin from pancreatic homogenate [ ] and thereby turned juvenile-onset (type 1) diabetes from a fatal to a manageable disease. Overshadowed by the monumental importance of this discovery was the observation that their insulin preparation first notably increased blood glucose before the much-heralded drop in glycemia was observed [ ]. In 1923, the same year in which Banting and Macleod were awarded the Nobel Prize in Medicine for their discovery, Charles Kimball and John Murlin identified this hyperglycemic factor and named it glucagon [ ]. Secreted from the pancreatic α-cells in negative correlation to blood glucose, glucagon acts on the liver to enhance de novo glucose production and to stimulate the breakdown of glycogen [ , , , , , , ]. Ever since, glucagon is largely recognized for its ability to oppose the hyperglycemic effects of insulin with therapeutic value largely restricted to treat severe hypoglycemia. This negative image of glucagon is further spurred by the demonstration that the inadequate postprandial suppression of glucagon secretion can contribute to hyperglycemia and the development of type 2 diabetes (T2D) [ , , , , ], whereas the blocking of glucagon action improves glucose metabolism in rodents, dogs, monkeys, and humans (as reviewed in [ ]). Stigmatized for being largely of diabetogenic nature, glucagon is a pleiotropic hormone with metabolic action that goes far beyond the regulation of blood glucose.