Incretin

Incretins are hormones from the gut that strengthen glucose-stimulated insulin secretion when nutrients enter via the oral route. The name derives from the incretin effect: glucose taken by mouth elicits a considerably bigger insulin response than an intravenous infusion adjusted to produce an identical blood glucose profile. In healthy human physiology, this amplification from the gut is responsible for about half to two-thirds of the insulin released after a meal.

GLP-1 and GIP

In humans, only two hormones fulfil the definition. GIP comes from K-cells in the duodenum; GLP-1 comes from L-cells located further down the gut. Each is a ligand of a class B GPCR, each enhances insulin secretion only while glucose is raised — the glucose dependence that makes incretin biology so appealing — and each is cut within minutes by dipeptidyl peptidase-4 at the alanine in second position.

Beating the DPP-4 clock

All engineered analogs in this class are designed to outrun that DPP-4 cleavage. Replacing the cleavage site with Aib or a D-amino acid and attaching a fatty-acid chain for albumin binding lengthens the half-life from minutes to days. When picking a comparator, the first thing to establish is which incretin receptor a research peptide acts on and with what relative potency.

Related terms

GLP-1 receptor agonist · dual agonist · amylin. Browse GLP-1 and incretin peptides or the GLP-1 / incretin pathway hub.