GIP (glucose-dependent insulinotropic polypeptide) is a 42-amino-acid hormone. K cells of the duodenum and proximal jejunum release it in response to food, mainly fat and carbohydrate [1][2]. Together with GLP-1 it is one of the incretins: gut hormones that amplify insulin secretion after a meal.
Receptor and effects
GIP binds the GIPR receptor, which couples to the G protein Gs. The receptor is found on pancreatic β cells, adipocytes, bone and parts of the brain [1][3]. In β cells GIP boosts insulin secretion only when glucose is elevated, so on its own it does not cause hypoglycaemia. In adipose tissue it takes part in fat storage, and its effect on α cells depends on glucose: at low glucose, GIP can raise glucagon secretion [3][4].
Stability in blood
The enzyme DPP-4 breaks down native GIP by removing two N-terminal residues, which inactivates the hormone. The half-life of native GIP is a few minutes [2][4]. Research analogues are therefore built to resist DPP-4 and carry a fatty-acid anchor that binds albumin.
Why GIP is back in focus
Interest in GIPR returned with co-agonists. Tirzepatide acts on GIPR and the GLP-1 receptor at once, and in a head-to-head phase 3 trial it beat semaglutide on HbA1c and body weight [6]. How much of the effect comes from GIPR itself is still debated: some work ties it to receptor agonism, some to antagonism [3][5].
Reference material. Not medical advice. The molecules mentioned are for laboratory research only (RUO).
See also: GLP-1, glucagon, comparison of the three axes.