GLUCAGON - NEW CONCEPTS ABOUT AN OLD HORMONE

Summary: Recent technical advances have led to a great increase in information regarding the role of glucagon in normal human physiology and in diabetes. In man, physiological actions appear to be limited to stimulation of hepatic glycogenolysis, gluconeogenesis, and possibly ketogenesis. Glucagon plays an important role (with insulin) to maintain basal hepatic glucose output and acts synergistically with catecholamines and Cortisol as a counter‐regulatory hormone in preventing hypoglycaemia. On the other hand glucagon is relatively unimportant (in contrast to insulin) in the assimilation of a glucose or carbohydrate load. Glucagon secretion is mainly controlled by the nervous system, both sympathetic and parasympathetic. Nervous control of the pancreatic A (glucagon‐releasing) cell is in turn modulated by plasma concentrations of glucose and other substrates and by hormonal influences. Circulating “glucagon” consists of several different peptides of varying molecular weight and differing biological activity. Also “glucagon” may be secreted by tissues other than the pancreas. Both the liver and kidney are important sites of metabolism of the various “glucagons”. Glucagon levels are raised in human diabetes mellitus. It appears that the hyper‐glucagonaemia in human diabetes is secondary to the diabetic state, rather than a primary defect of the A cell. Glucagon may accentuate hyperglycaemia and ketogenesis but is not essential for the development of the diabetic state. A clinical syndrome of excess glucagon production from an islet cell tumour (glucagonoma) has recently been defined. Diabetes, though common, is not always present and the most prominent clinical feature is an unusual skin rash, migratory necrolytic erythema. Pharmacological doses of glucagon have a wide range of effects in humans. In addition to treating hypoglycaemia, glucagon may be used as an inotropic cardiac stimulant, or to inhibit gastrointestinal motility during endoscopy. Other suggested uses are mainly related to tests of endocrine function. Copyright © 1979, Wiley Blackwell. All rights reserved