Insulinotropic effect of endogenous incretins is greater after gastric bypass than sleeve gastrectomy despite diminished beta-cell sensitivity to plasma incretins.

Glycemic effects of gastric bypass (GB) and sleeve gastrectomy (SG) is attributed to rapid nutrient flux and enhanced insulinotropic effects of gut hormones but β-cell sensitivity to GLP-1 or GIP is diminished after GB. Post-OGTT β-cell sensitivity to enhanced incretins by DPP4i is markedly reduced in bariatric subjects versus non-operated controls, and yet insulin secretory response (disposition index) is increased leading to hypoglycemia in GB and not SG. Blunted sensitivity to GLP-1 may represent β-cell adaptation to massive elevation in GLP-1 secretion following bariatric surgery to protect against hypoglycemia.The differential effect of enhanced concentrations of incretins on post-OGTT insulin response (disposition index) among GB versus SG highlights a distinct adaptive process among the two procedures.Augmented insulinotropic effects of gut hormones on postprandial insulin secretory response after GB despite a reduced beta-cell sensitivity to plasma concentrations of GLP-1 makes a case for non-hormonal mechanisms of GLP-1 action after GB.Better understanding of long-term effects of bariatric surgery on gut-pancreas axis activity is critical in development of GLP-1-based strategies to address glucose abnormalities (both hyperglycemia and hypoglycemia) in these settings.