Effect of Bariatric Surgery on Incretin Function

Abstract

The gut hormone incretins play a preponderant physiological role in glucose-stimulated insulin release during meals. Although weight loss is a key determinant of diabetes remission after bariatric surgery, the incretin hormones may also play a role in glucose control. After gastric bypass (RYGBP), the release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced. The rapid transit of food from the gastric pouch to the distal jejunum and ileum is responsible for the greater GLP-1 release after RYGBP. The exaggerated release of GLP-1 boosts insulin secretion and lowers postprandial glucose levels during meals. The incretin effect on insulin secretion, or the greater insulin response to oral glucose compared to an isoglycemic intravenous glucose challenge, is severely impaired in patients with diabetes, but is recovered rapidly after RYGBP. The improvement in insulin secretion rate and beta cell sensitivity to oral glucose after RYGBP is mediated by endogenous GLP-1, and is abolished by exendin 9-39, a specific GLP-1 receptor antagonist. While calorie restriction and weight loss have major effects on the rapid and sustained improvement of fasted glucose metabolism, the enhanced incretin effect is a key player of postprandial glucose control after RYGBP.