Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone released from the gastrointestinal tract and was first found to inhibit the secretion of hydrochloric acid from stomach parietal cells. GIP also stimulates postprandial insulin secretion from pancreatic β-cells following a pathway activated by the binding of GIP to its specific receptor thus making GIP, along with GLP-1, a major potentiator of glucose induced insulin secretion¹.

The human GIP receptor is a 466 amino-acid G-coupled protein receptor that is 81.5% and 81.2% identical to the hamster and rat receptors comprising seven potential transmembrane domains. This property is shared with glucagon and secretin receptor families.

GIP has an affinity of K_d~0.2 nM to its receptor. GIPR activates several intracellular pathways including MAP kinase, phospholipase A2 but primarily activates adenylyl cyclase causing an increase in cAMP. GIP has been also found to be expressed outside the gut in organs such as the heart, brain and adipose tissue.

In patients with Type 2 Diabetes-Mellitus, GIP levels are normal or at most minimally reduced therefore suggesting that there is a resistance of β-cells to GIP caused by a change in receptor expression signaling or mutation. In addition, mice whose GIPR gene expression is disrupted, following three months of high fat feeding, show reduced weight gain and adipose tissue compared to regular mice suggesting the elimination of this receptor may protect against the onset of severe obesity².