Glucose intolerance caused by a defect in the entero-insular axis: A studyin gastric inhibitory polypeptide receptor knockout mice

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) r eceptor gene (GIPR) were generated to determine the role of GIP as a mediat or of signals from the gut to pancreatic beta cells, GIPR-/- mice have high er blood glucose levels with impaired initial insulin response after oral g lucose load. Although blood glucose levels after meal ingestion are not inc reased by high-fat diet in GIPR+/+ mice because of compensatory higher insu lin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by CIP determines glucose tolerance after oral glucose load in vivo, and b ecause GIP plays an important role in the compensatory enhancement of insul in secretion produced by a high insulin demand, a defect in this entero-ins ular axis may contribute to the pathogenesis of diabetes.