Effect of glucagon on carbohydrate-mediated secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1).
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.
Ranganath
L
L
Department of Biochemistry, Epsom General Hospital, Epsom KT18 7EG, UK.
Schaper
F
F
Gama
R
R
Morgan
L
L
Wright
J
J
Teale
D
D
Marks
V
V
D000082:Acetaminophen / Q000494:pharmacology; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002241:Carbohydrates / Q000502:physiology*; D005746:Gastric Emptying / Q000187:drug effects; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005765:Gastrointestinal Agents / Q000097:blood / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood* / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D010865:Pilot Projects; D011498:Protein Precursors / Q000097:blood*; D016037:Single-Blind Method
D018712:Analgesics, Non-Narcotic; D001786:Blood Glucose; D002241:Carbohydrates; D005765:Gastrointestinal Agents; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D000082:Acetaminophen; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose