Recognition of the importance of gut hormones in the insulin response to feeding was quickly followed by isolation of the first incretin, gastric inhibitory polypeptide (GIP). This 42 amino acid peptide, together with it’s sister incretin hormone glucagon-like peptide 1 (GLP-1), is released into blood following feeding and exerts various actions on nutrient homeostasis despite rapid degradation by the enzyme dipeptidyl peptidase-4 (DPP-4). GIP acts in several distinct ways to lower blood glucose, the most notable being stimulation of insulin secretion. Insulin release occurs in a glucose-dependent manner, serving to minimise the risk of hypoglycaemia. GIP also enhances the growth, differentiation, proliferation and survival of pancreatic beta cells. These actions are complemented by effects in peripheral tissues including inhibition of hepatic glucose production, depression of insulin clearance and promotion of glucose uptake. Recently, other important and initially unsuspected actions have been uncovered for GIP, including central neuroprotection and promotion of bone formation. However, particularly interesting is the finding of GIP receptors on adipocytes and appreciation that GIP secreted strongly in response to fat ingestion may be involved in translation of excessive amounts of dietary fat into adipocyte tissue stores. Established effects of GIP on adipocytes include increase of lipoprotein lipase, stimulation of lipogenesis, enhancement of fatty acid and glucose uptake, augmentation of insulin-induced fatty acid incorporation and inhibition of both glucagon- and adrenergic receptor mediated lipolysis. These actions open up an unexpected therapeutic channel of exploiting GIP receptor antagonism for treatment of obesity and associated insulin resistance. This scenario is borne out by studies in high fat fed mice or ob/ob mice with either genetic knock-out of GIP receptor or diminished GIP action. Further studies are needed to evaluate the applicability to human obesity-diabetes. However, rapid cure of diabetes in grossly obese subjects undergoing Roux-en Y bypass surgery may be partly mediated by surgical bypass of GIP secreting K-cells in upper small intestine. This operation results in altered patterns of gherlin and GLP-1, but also low levels of circulating GIP with restoration of normoglycaemia due to substantial improvement of insulin resistance and beta cell glucose responsiveness.