Gastric Inhibitory Polypeptide (GIP)
A 42 amino acid incretin hormone produced by intestinal K-cells that stimulates insulin secretion and influences fat metabolism. GIP acts through the GIP receptor, which is co-targeted alongside the GLP-1 receptor by tirzepatide. The role of GIP in weight management is an active area of research.
Technical Context
GIP (42 aa) is secreted from K-cells in the duodenum and proximal jejunum in response to glucose and fat ingestion. The GIP receptor (GIPR) is a class B GPCR expressed on pancreatic beta cells, adipocytes (where it promotes lipogenesis and adipocyte differentiation), osteoblasts (promoting bone formation), and brain neurons (where it may regulate appetite). In type 2 diabetes, GIP's insulinotropic effect is impaired despite normal or increased GIP secretion — this GIP resistance partly explains why DPP-4 inhibitors (which raise both GLP-1 and GIP) produce smaller insulin responses than GLP-1 RAs. Tirzepatide's GIP agonism may work through different mechanisms than native GIP, potentially resensitising the GIP signalling pathway. Research into GIP receptor biology is evolving rapidly.