Glucose-dependent insulinotropic polypeptide (revision 7)

Glucose-dependent insulinotropic polypeptide (GIP), also termed glucose-dependent insulinotropic peptide, is a 42-residue peptide hormone secreted by enteroendocrine K cells of the duodenum and proximal jejunum in response to the ingestion of glucose, fat and amino acids. It is one of the two principal incretin hormones, the other being Glucagon-like peptide-1 (GLP-1).^[1]

GIP is processed post-translationally from pro-GIP and circulates in two forms: the active GIP (1–42) and an N-terminally cleaved GIP (3–42) produced by dipeptidyl peptidase-4 cleavage. Both forms retain insulin-secretory activity, which is unusual among incretin peptides and is the basis for the glucose-dependent descriptor — GIP potentiates insulin secretion only when glucose is elevated.^[2]

GIP is encoded by the GIP gene and is processed from a 153-residue pro-GIP. Like GLP-1, it is subject to tissue-specific post-translational modification. In K cells, endopeptidases cleave pro-GIP to release the active hormone. The principal stimuli are glucose and long-chain fatty acids; amino acids are a weaker stimulus.^[1]

K cells are found predominantly in the duodenum and jejunum, extending into the ileum in smaller numbers. They are open-type epithelial cells with an apical surface exposed to the lumen, allowing direct contact with nutrient-induced secretagogues. Secretion is biphasic: an early phase within 15 minutes of ingestion, followed by a later more sustained phase as nutrients pass through the intestine.^[1]