Gastric inhibitory polypeptide (GIP), also known as glucose-dependent insulinotropic polypeptide, is a member of the secretin/glucagon superfamily of peptides. It is a well conserved 42 amino acid peptide generated by post-translational cleavage of the precursor protein proGIP (1).
GIP is synthesized by enteroendocrine K cells of the small intestine, found in highest concentration in the duodenum. It is released into the circulation in response to glucose or fat ingestion (1). A short but bioactive form of GIP (GIP1-30) is secreted from pancreatic alpha-cells within the pancreatic islets (2). In the CNS, GIP is expressed in several brain regions including the cerebral cortex, hippocampus, and olfactory bulb (3).
GIP exerts its effects via interaction with its G-protein-coupled receptor. In pancreatic beta-cells, it increases adenylyl cyclase activity, thereby stimulating insulin secretion (1,2). GIP is also implicated in the control of lipid metabolism and the development of obesity. In adipose tissue, it increases lipoprotein lipase activity and lipogenesis (1,4). Recently, GIP appeared as a major player in bone metabolism and bone cell physiology by preserving bone strength (4,5). In the brain, GIP induces neuronal progenitor cell proliferation and has a neuroprotective function (3).