Glucagon and Glucagon-Like Peptides–Animals
The Role of GLP-1 Receptor Signaling in Metabolic Changes after Roux-en-Y Gastric Bypass in Diet Induced Obese Rats
6/10/2012 9:30:00 AM
6/10/2012 9:45:00 AM
, ERIC P. SMITH, TODD GREER, JOSE BERGER, DAVID A.. D'ALESSIO,
Roux-en-Y gastric bypass (RYGB) is the gold-standard for bariatric surgery, and leads to sustained weight loss and rapid resolution of diabetes. RYGB is associated with an elevated postprandial secretion of glucagon-like peptide-1 (GLP-1), which has been proposed to mediate some of the metabolic improvements following RYGB. The present study sought to determine whether GLP-1 receptor signaling is required for the effects of RYGB on glucose homeostasis, food intake, and weight loss. Diet-induced obese rats had RYGB or sham surgeries, and were randomly allocated to chronic blockade of GLP-1 action by minipump infusion of the GLP-1 receptor antagonist Exendin-9,39 (Ex-9; 2 pmol/kg/min), or vehicle (Vh). Minipumps were implanted subcutaneously at the time of RYGB or sham operation and delivered treatment for 6 weeks. The four groups, sham-Vh (n=5), sham-Ex9 (n=4), RYGB-Vh (n=6) and RYGB-Ex9 (n=8) were tracked for food intake and body weight daily for 6 weeks. At 6 weeks, an oral glucose tolerance test (OGTT; 1.5g glucose/kg b.w.) was performed. RYGB led to a ~11% and 18% reduction of body weight and accumulative food intake, respectively, and these effects did not differ between Vh and Ex-9 treated rats. In sham rats, Ex-9 treatment led to a ~19% increase in the glucose AUC during the OGTT. In contrast, after RYGB, Ex-9 caused a ~99% increase (p<0.05) in glucose AUC. These results demonstrate that GLP-1 action has a disproportionate effect on the maintenance of glucose homeostasis following RYGB in diet induced obese rats. In contrast, increased postprandial GLP-1 is less likely to play a role in alteration of food intake and body weight after this procedure.
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