gastric inhibitory peptide

GIP is released from duodenal and jejunal K cells in response to fatty acids, amino acids, and oral glucose. It is one of the two main incretins (along with GLP-1) responsible for the 'incretin effect'—the phenomenon whereby oral glucose administration produces a greater insulin response than IV glucose at equivalent blood glucose levels, due to gut hormone potentiation of insulin secretion. GIP acts on pancreatic beta cells via a GIP receptor coupled to Gs protein, increasing intracellular cAMP and enhancing glucose-dependent insulin secretion. Unlike GLP-1, GIP has minimal effect on glucagon secretion, gastric emptying, or satiety, and its name (originally 'gastric inhibitory peptide') reflects early observations that pharmacologic doses inhibit gastric acid secretion and gastric emptying, though this is not a major physiologic action at normal levels. Clinically, GIP is relevant in type 2 diabetes mellitus, where the incretin effect is blunted, partly due to beta-cell GIP resistance. This has led to development of dual GIP/GLP-1 receptor agonists (e.g., tirzepatide) for type 2 diabetes and obesity management, which produce superior glycemic control and weight loss compared to GLP-1 agonists alone. GIP is degraded rapidly by the enzyme DPP-4, similar to GLP-1, which is why DPP-4 inhibitors (gliptins) prolong incretin activity and are used as antidiabetic agents.