Incretin effect (GIP and GLP-1)

The incretin effect is the observation that oral glucose ingestion triggers a larger insulin secretory response than an equivalent intravenous glucose infusion — a difference attributed to gut-derived peptides called incretins. The principal incretins are glucagon-like peptide-1 (GLP-1), released by L-cells in the distal small intestine and colon, and glucose-dependent insulinotropic polypeptide (GIP), released by K-cells in the proximal small intestine; together they account for 50–70 % of postprandial insulin output in healthy individuals (Baggio & Drucker, 2007). Both act on G-protein-coupled receptors on pancreatic β-cells to augment insulin release; GLP-1 also suppresses glucagon and slows gastric emptying. In type 2 diabetes the incretin effect is substantially diminished — principally because GIP loses insulinotropic potency at the β-cell level, while GLP-1 secretion is only modestly reduced (Nauck & Meier, 2016). GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists have reduced cardiovascular events and all-cause mortality in high-risk T2D cohorts. Whether endogenous incretin tone predicts aging trajectories in metabolically healthy individuals remains an open question; evidence to date derives primarily from T2D intervention trials (Nauck & Müller, 2023).