GIP's involvement in the pathophysiology of type 2 diabetes.

During the past four decades derangements in glucose-dependent insulinotropic polypeptide (GIP) biology has been viewed upon as contributing factors to various parts of the pathophysiology type 2 diabetes. This overview outlines and discusses the impaired insulin responses to GIP as well as the effect of GIP on glucagon secretion and the potential involvement of GIP in the obesity and bone disease associated with type 2 diabetes. As outlined in this review, it is unlikely that the impaired insulinotropic effect of GIP occurs as a primary event in the development of type 2 diabetes, but rather develops once the diabetic state is present and beta cells are unable to maintain normoglycemia. In various models, GIP has effects on glucagon secretion, bone and lipid homeostasis, but whether these effects contribute substantially to the pathophysiology of type 2 diabetes is at present controversial. The review also discusses the substantial uncertainty surrounding the translation of preclinical data relating to the GIP system and outline future research directions.