GIP (Glucose-Dependent Insulinotropic Peptide)
Metabolic / DiabetesAlso known as: Glucose-Dependent Insulinotropic Peptide, Gastric Inhibitory Peptide, Incretin
Mechanism
GIP is one of the two incretin hormones (alongside GLP-1) — released from K cells in the upper intestine after eating, it stimulates insulin secretion in a glucose-dependent manner. GIP is responsible for roughly 50-70% of the incretin effect. It is the "other half" of dual incretin therapy — tirzepatide (Mounjaro) works by activating both GIP and GLP-1 receptors, which is why it is so effective for weight loss and diabetes.
Technical detail
GIP is a 42-amino-acid peptide released from duodenal/jejunal K cells in response to nutrients (especially fat and glucose). It binds GIPR (Gs-coupled GPCR) on pancreatic beta cells, activating adenylyl cyclase-cAMP-PKA/Epac2 signaling to potentiate glucose-stimulated insulin secretion (GSIS). GIP also promotes beta cell proliferation and survival via CREB and PI3K-Akt pathways. In adipose tissue, GIPR activation promotes lipogenesis and fat storage. The role of GIPR in weight loss is complex: both agonism (tirzepatide) and antagonism show anti-obesity effects, suggesting receptor desensitization or biased signaling may be involved. GIP is rapidly inactivated by DPP-4 (half-life ~5 min).
Evidence
- moderate
Glucose-dependent insulinotropic polypeptide (GIP): anti-diabetic and anti-obesity potential?
Victor A Gault et al. (2003) — Neuropeptides — PMID: 14607102
Review summarizes GIP as an insulinotropic incretin with short native half-life and highlights development of enzyme-resistant super-GIP analogues with anti-diabetic activity, while also noting links between GIP signaling, overnutrition, and obesity-related metabolic disease.