The effects of gastric inhibitory polypeptide (GIP) on glucose and lipid metabolism of isolated rat adipocytes were investigated. In a dose-dependent manner, GIP stimulated 2-deoxy-glucose uptake increasing the glucose transport rate by up to 140% at a concentration of 10(-7) mol/l. GIP also stimulated the conversion of 14C-glucose into extractable lipids by up to 81% at 10(-7) mol/l. Insulin-stimulated 2-deoxy-glucose uptake and lipogenesis were additively enhanced by the presence of GIP. Insulin binding was slightly but not significantly increased by addition of GIP, mainly due to an increase in receptor affinity. GIP had a weak lipolytic activity, but lipolysis elicited by glucagon or isoproterenol was potently reduced. In conclusion, independent of its insulinotropic action, GIP showed a insulin-like activity on glucose metabolism and lipolysis in rat adipose tissue. The possible role of GIP for the development of obesity is discussed.