Enhanced postprandial glucagon-like peptide-1 secretion during obesity development has a protective role against glucose intolerance induction in rats

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glycaemic response by enhancing insulin secretion. We previously demonstrated that the postprandial GLP-1 response was enhanced during the development of diet-induced obesity in rats. However, the physiological relevance of the enhanced GLP-1 response remained unclear. We aimed to determine the role of endogenous GLP-1 during obesity development. Male Sprague-Dawley rats were given either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose, weight basis) diet with or without continuous administration of the GLP-1 receptor antagonist, exendin (9-39) (Ex9, 100 mu g/d), for 5 weeks. Meal tolerance tests (MTT) were performed to assess postprandial glucose, insulin and GLP-1 responses to a liquid diet administration (15 kcal (63 kJ)/10 ml per kg body weight) every 2 weeks. The AUC of postprandial glucose in the HFS group was similar to the control group in both MTT (P = 0 center dot 9665 and P = 0 center dot 3475, respectively), whereas AUC of postprandial GLP-1 (after 4 weeks,P = 0 center dot 0457) and of insulin (after 2 and 4 weeks, P = 0 center dot 0486 and P = 0 center dot 0110) was higher in the HFS group compared with the control group. In the Ex9 group, AUC of postprandial glucose (P = 0 center dot 0297 and P = 0 center dot 0486) was higher along with a lower insulin response compared with the HFS group (P = 0 center dot 0564 and P = 0 center dot 0281). These results suggest that enhancement of the postprandial GLP-1 response during obesity development has a role in maintaining a normal postprandial glycaemic response. Hence, enhancing endogenous GLP-1 secretion by certain materials could be a potential target for prevention of glucose intolerance.