incretin

Incretins are intestinal hormones that augment insulin secretion in response to oral nutrient intake. The two best characterized incretins are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). GIP is secreted by K cells in the proximal small intestine, while GLP-1 is produced by L cells in the distal small intestine and colon. When nutrients enter the gut, GIP and GLP-1 are released into the bloodstream and stimulate pancreatic beta cells to secrete insulin in a glucose-dependent manner. They also suppress inappropriate glucagon release, slow gastric emptying, and, for GLP-1, promote satiety. The collective action of these hormones contributes to the incretin effect, whereby oral glucose elicits a greater insulin response than an equivalent amount of intravenous glucose.

Incretins are rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), which gives them short circulating half-lives. Therapeutically, incretin-based drugs include GLP-1 receptor agonists (injectable) and DPP-4 inhibitors (oral). GLP-1 receptor agonists, such as exenatide, liraglutide, dulaglutide and semaglutide, enhance GLP-1 signaling, improve glycemic control, and often lead to weight loss. DPP-4 inhibitors, such as sitagliptin and vildagliptin, increase endogenous levels of GIP and GLP-1, thereby enhancing insulin secretion. Potential adverse effects include nausea and, with some agents, an elevated risk of pancreatitis; certain GLP-1 therapies carry warnings about thyroid C-cell tumors from animal studies, though human risk remains unclear and these drugs have contraindications in individuals with a history of medullary thyroid carcinoma or MEN2.

Overall, incretins play a key role in postprandial glucose regulation and are central to modern diabetes management.