Clinical Information

Glucagon is a single-chain polypeptide of 29 amino acids that is derived from a larger precursor peptide (big plasma glucagon), which is cleaved upon secretion. The main sites of glucagon production are the hypothalamus and pancreatic alpha-islet cells. The function of hypothalamic glucagon is incompletely understood and currently no clinical disorders of hypothalamic glucagon function have been defined. Pancreatic islet glucagon is secreted in response to hypoglycemia, with resultant increases in blood glucose concentration. Glucagon's hyperglycemic effect is produced by stimulating hepatic glycogenolysis and gluconeogenesis; it has no effect on muscle glycogen. Once blood glucose levels have normalized, glucagon secretion ceases.

Excessive glucagon secretion can lead to hyperglycemia. Excessive and inappropriate glucagon secretion can sometimes be observed in diabetes, particularly during ketoacidosis, and can complicate management of the disorder. In rare cases, it also can occur in tumors of the pancreatic islets (glucagonoma), hepatocellular carcinomas, carcinoid tumors, and other neuroendocrine neoplasms. Patients with glucagon-secreting tumors may present with classic glucagonoma syndrome, consisting of necrolytic migratory erythema, diabetes, and diarrhea, but can also have more subtle symptoms and signs.

Decreased or absent glucagon response to hypoglycemia can be seen in type I diabetes (insulin-dependent diabetes) and can contribute to severe and prolonged hypoglycemic responses.

Glucagon is routinely measured along with serum glucose, insulin, and C-peptide levels during the mixed-meal test employed in the diagnostic workup of suspected postprandial hypoglycemia. However, it plays only a minor role in the interpretation of this test.