GIP increases insulin receptor affinity and cellular sensitivity in adipocytes.

Glucose ingestion has been previously shown to rapidly increase both the affinity of the insulin receptor and the cellular sensitivity of target tissues for insulin. We now demonstrate that gastric inhibitory polypeptide (GIP), a gastrointestinal hormone released by glucose ingestion, can mimic these effects in vitro. Incubation of rat adipocytes with GIP (10-100 ng/ml) resulted in both a displacement to the left of the insulin binding isotherm (i.e., increased receptor affinity) and potentiated insulin-mediated glucose uptake at insulin concentrations less than 1 ng/ml (i.e., increased cellular insulin sensitivity). Cholecystokinin, another gastrointestinal hormone, did not alter the insulin receptor binding characteristics or glucose uptake of the adipocytes in vitro. We suggest that GIP, a known potentiator of glucose-stimulated insulin secretion, may also modulate the effects of insulin by directly altering target tissue sensitivity to insulin.