Incretin pathway

The incretin pathway is a physiological system responsible for the amplification of insulin secretion following oral nutrient intake, mediated primarily by the hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) [StatPearls, NBK551568]. These hormones bind to their respective G protein-coupled receptors on pancreatic beta cells to stimulate insulin release in a glucose-dependent manner, while GLP-1 also suppresses glucagon secretion from alpha cells [PubMed, 21846255]. Beyond the pancreas, the pathway influences gastric emptying and central satiety centers, contributing to weight regulation and cardiovascular health [Nature Reviews Endocrinology, 10.1038/nrendo.2012.39]. In patients with type 2 diabetes, the incretin effect is significantly blunted, leading to the development of several drug classes that either mimic these hormones or prevent their degradation by the enzyme dipeptidyl peptidase-4 (DPP-4) [NIH, PMC3153004]. Modern therapeutics targeting this pathway, such as GLP-1 receptor agonists and dual GLP-1/GIP agonists, have become cornerstones in the management of diabetes and obesity due to their potent glucose-lowering and weight-loss effects.

Other names

Incretin systemIncretin axisGLP-1/GIP signaling pathwayEntero-insular axis

Activation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors to enhance glucose-dependent insulin secretion and suppression of glucagon, or inhibition of dipeptidyl peptidase-4 (DPP-4) to increase endogenous incretin levels.