Surgical control of obesity and diabetes: the role of intestinal vs. gastric mechanisms in the regulation of body weight and glucose homeostasis.

OBJECTIVE

To elucidate the specific role of gastric vs. intestinal manipulations in the regulation of body weight and glucose homeostasis.

DESIGN AND METHODS

The effects of intestinal bypass alone (duodenal-jejunal bypass -DJB) and gastric resection alone (SG) in Zucker Diabetic Fatty (ZDF) rats were compared. Additional animals underwent a combination procedure (SG + DJB). Outcome measures included changes in weight, food intake (FI), oral glucose tolerance (GT) and gut hormones.

RESULTS

DJB did not substantially affect weight and FI, whereas SG significantly reduced weight gain and food consumption. DJB rats showed weight-independent improvement in GT, which improved less after SG. Furthermore, SG significantly suppressed plasma ghrelin and increased insulin, glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide and peptide YY response to oral glucose whereas DJB had no effects on postprandial levels of these hormones. DJB restored postprandial glucagon suppression in diabetic rats whereas SG did not affect glucagon response. The combination procedure (SG + DJB) induced greater weight loss and better GT than SG alone without reducing food intake further.

CONCLUSIONS

These findings reveal a dominant role of the stomach in the regulation of body weight and incretin response to oral glucose whereas intestinal bypass primarily affects glucose homeostasis by a weight-, insulin- and incretin-independent mechanism.