Effect of glucagon on carbohydrate-mediated secretion of glucose-dependentinsulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1)
L. Ranganath et al., Effect of glucagon on carbohydrate-mediated secretion of glucose-dependentinsulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1), DIABET M R, 15(6), 1999, pp. 390-394
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.