Enteroendocrine secretion of gut hormones in diabetes, obesity and after bariatric surgery

Gastric bypass surgery is associated with a major weight loss and often causes remission in patients with type 2 diabetes. Surgery is also associated with dramatic increases in the secretion of the gut hormones, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), both of which regulate appetite and food intake, while GLP-1 in addition functions as an incretin hormone, stimulating insulin secretion. It has been possible to probe the role of GLP-1 for the diabetes resolution after gastric bypass using a GLP-1 receptor antagonist, and it is clear that the enhanced beta cell sensitivity to glucose which underlies the enhanced insulin secretion in the patients after the operation depends critically on the increased GLP-1 secretion. Both hormones seem to contribute importantly to the reduction in food intake after bypass and, therefore, to the weight loss. Currently, there are no data to indicate that decreased secretion of the hormones is involved in the pathogenesis of obesity and/or diabetes, but impaired secretion generally observed in obesity (and hence also in diabetes) may contribute to the development. Because of these effects receptor agonists for both hormones are currently being developed for the treatment of obesity and diabetes.