Effect of glucagon on carbohydrate-mediated secretion of glucose-dependentinsulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1)

Background The insulinotropic hormones, glucose-dependent insulino-tropic p olypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1), regulate insulin secretion to nutrient intake and constitute the endocrine arm of t he entero-insular axis. Glucagon has been implicated in the pathophysiology of conditions characterised by abnormal glucose tolerance such as obesity and diabetes mellitus although its effect on the entero-insular axis is not fully understood. Materials and methods We investigated the effect of: exogenous glucagon on the entero-insular axis and its relation to gastric emptying in six healthy men aged [mean (+/-S.E.M.)] 23.6 (0.9) years with a body mass index of 24. 0 (1.5) kg/m(2). Plasma glucose, GIP, GLP-1, insulin and paracetamol concen trations were measured before and after a 100 g oral carbohydrate load cont aining 1.5 g of paracetamol for 6 h during intravenous infusion of either g lucagon or saline. Results When compared to the saline infusion, peak and integrated insulin a nd glucose concentrations were higher (p < 0.05) following glucagon infusio n. After 60 min paracetamol concentrations were lower (p < 0.05) following glucagon infusion. Integrated responses for GIP and GLP-1 were markedly red uced following glucagon infusion. Conclusions Exogenous glucagon in addition to its well-documented action of increasing glucose and insulin concentrations and delaying gastric emptyin g also markedly reduces GIP and GLP-1 secretion. The inhibition of GLP-1 so on after commencement of glucagon infusion supports a direct effect of gluc agon on intestinal L-cells. We speculate that the marked inhibition of post prandial GLP-1 secretion by glucagon may be of importance in the pathogenes is of relative insulinopenia in Type 2 diabetes and in the development of r educed satiety in obesity and diabetes. Copyright (C) 1999 John Wiley & Son s, Ltd.