A Synergy between Incretin Effect and Intestinal Gluconeogenesis Accounting for the Rapid Metabolic Benefits of Gastric Bypass Surgery

The early improvement of glucose control taking place shortly after gastric bypass surgery in obese diabetic patients has long been mysterious. A recent study in mice has highlighted some specific mechanisms underlying this phenomenon. The specificity of gastric bypass in obese diabetic mice relates to major changes in the sensations of hunger and to rapid improvement of glucose parameters. The induction of intestinal gluconeogenesis plays a major role in diminishing hunger, and in restoring insulin sensitivity of endogenous glucose production. In parallel, the restoration of the secretion of glucagon-like peptide 1 and insulin plays a key additional role, in this context of recovered insulin sensitivity, to improve postprandial glucose tolerance. Therefore, a synergy between an incretin effect and intestinal gluconeogenesis is a key feature accounting for the rapid improvement of glucose control in obese diabetic patients after bypass surgery.