Background:
The insulinotropic hormones, glucose-dependent insulinotropic polypeptide (gip) and glucagon-like peptide-1 (7-36 amide) (glp-1), regulate insulin secretion to nutrient intake and constitute the endocrine arm of the 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 concentrations were measured before and after a 100 g oral carhohydrate load containing 1.5 g of paracetamol for 6 h during intravenous infusion of either glucagon or saline.
Results:
When compared to the saline infusion, peak and integrated insulin and glucose concentrations were higher (p<0.05) following glucagon infusion. after 60 min paracetamol concentrations were lower (p<0.05) following glucagon infusion. integrated responses for gip and glp-1 were markedly reduced following glucagon infusion.
Conclusions:
Exogenous glucagon in addition to its well-documented action of increasing glucose and insulin concentrations and delaying gastric emptying also markedly reduces gip and glp-1 secretion. the inhibition of glp-1 soon after commencement of glucagon infusion supports a direct effect of glucagon on intestinal l-cells. we speculate that the marked inhibition of postprandial glp-1 secretion by glucagon may be of importance in the pathogenesis of relative insulinopenia in type 2 diabetes and in the development of reduced satiety in obesity and diabetes.