Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.

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 µg/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 = 0·9665 and P = 0·3475, respectively), whereas AUC of postprandial GLP-1 (after 4 weeks,P = 0·0457) and of insulin (after 2 and 4 weeks, P = 0·0486 and P = 0·0110) was higher in the HFS group compared with the control group. In the Ex9 group, AUC of postprandial glucose (P = 0·0297 and P = 0·0486) was higher along with a lower insulin response compared with the HFS group (P = 0·0564 and P = 0·0281). 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.

Obesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding. Nine healthy individuals (five males, four females) performed a mixed meal tolerance test (MTT) before and after consuming a high-fat (65 %), high-energy (+50 %) diet for 7 d. Measurements of plasma glucose, NEFA, acylated ghrelin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and serum insulin were taken before (fasting) and at 30-min intervals throughout the 180-min MTT (postprandial). Body mass increased by 0·79 (sem 0·14) kg after high-fat overfeeding (P<0·0001), and BMI increased by 0·27 (sem 0·05) kg/m2 (P=0·002). High-fat overfeeding also resulted in an 11·6 % increase in postprandial glucose AUC (P=0·007) and a 25·9 % increase in postprandial insulin AUC (P=0·005). Acylated ghrelin, GLP-1 and GIP responses to the MTT were all unaffected by the high-fat, high-energy diet. These findings demonstrate that even brief periods of overeating are sufficient to disrupt glycaemic control. However, as the postprandial orexigenic (ghrelin) and anorexigenic/insulintropic (GLP-1 and GIP) hormone responses were unaffected by the diet intervention, it appears that these hormones are resistant to short-term changes in energy balance, and that they do not play a role in the rapid reduction in glycaemic control.

Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity.