GIP biology and fat metabolism

The gastrointestinal hormone, gastric inhibitory polypeptide (GIP), is synt hesized and released from the duodenum and proximal jejunum postprandially. Its release depends upon several factors including meal content and pre-ex isting health status tie. obesity, diabetes, age; etc. It was initially dis covered and named for its gastric acid inhibitory properties. However, its more physiologically relevant role appears to be as an insulinotropic agent with a stimulatory effect on insulin release and synthesis. Accordingly, i t was later renamed glucose-dependent insulinotropic polypeptide because it s action on insulin release depends upon an increase in circulating levels of glucose. GIP is considered to be one of the principle incretin factors o f the enteroinsular axis. The GIP receptor is a G-protein-coupled receptor belonging to the family of secretin/VIP receptors. GIP receptor mRNA is wid ely distributed in peripheral organs, including the pancreas, gut, adipose tissue; heart, adrenal cortex, and brain, suggesting it may have other func tions in addition to the ones mentioned above. An overactive enteroinsular axis has been suggested to play a role in the pathogenesis of diabetes and obesity. In addition to stimulating insulin release, GIP has been shown to amplify the effect of insulin on target tissues. In adipose tissue, GIP has been reported to (1) stimulate fatty acid synthesis, (2) enhance insulin-s timulated incorporation of fatty acids into triglycerides, (3) increase ins ulin receptor affinity, and (4) increase sensitivity of insulin-stimulated glucose transport. In addition, although controversial, lipolytic propertie s of GIP have been proposed. The mechanism of action of GTP-induced effects on adipocytes is unknown, and it is unclear whether these effects of GIP o n adipocytes are direct or indirect. However, there is now evidence that GI P receptors are expressed on adipocytes and that these receptors respond to GIP stimulation. Given the location of its release and the timing of its r elease, GIP is an ideal anabolic agent and expanding our understanding of i ts physiology will be needed to determine its exact role in the etiology of diabetes mellitus and obesity.