Glucagon and diabetes mellitus.
The present status of knowledge about glucagon pathophysiology in diabetes is reviewed. 1) A-cells behave abnormally in all varieties of diabetes mellitus, spontaneous and experimental, except perhaps in case of pancreatectomized humans. These abnormalities are : hyperreactivity of A-cells to arginine, non suppressibility by glucose, and absence of stimulation following hypoglycemia. 2) These abnormalities appear as secondary in most instances : a) A-cells behave in a normal way in most studies with prediabetics ; b) plasma glucagon concentration is normalized by excellent control of diabetes or following prolonged insulin infusion. High doses of insulin are required most of the times to obtain a normalization of A-cell function : in insulin-dependent diabetics, the physiological portoperipheral insulin gradient no longer exists, and the high doses of insulin which are necessary may be the only mean to reconstitute the high insulin concentrations supposed to be present at the A-cell level. 3) Conflicting results have been collected about the role of this glucagon excess in aggravating the diabetic metabolic syndrome. Evanescent effects follow sustained glucagon infusions: but in diabetics, glucagon bursts rather than permanent hyperglucagonemia are observed and these appear deleterious to glucose tolerance. It seems clear however that insulin deprivation is required for the full expression of the consequences of glucagon excess.
D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D005934:Glucagon / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000502:physiology / Q000503:physiopathology; D010179:Pancreas / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D011236:Prediabetic State / Q000503:physiopathology; D013004:Somatostatin / Q000494:pharmacology
D007328:Insulin; D013004:Somatostatin; D005934:Glucagon