Glucometabolic gut hormones: beyond the incretin effect

The incretin effect refers to the enhanced insulin secretion in response to oral or enteric glucose. More specifically, the incretin effect designates the augmentation of insulin secretion after oral administration of glucose compared with insulin secretion levels observed after intravenous glucose administered to mimic the plasma glucose excursion elicited by the oral load [1–4]. The incretin effect is due to hormones secreted from the intestine, the most important ones being glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both these hormones stimulate pancreatic insulin secretion. GLP-1, in addition, exerts suppressive effects on pancreatic glucagon secretion, gastrointestinal motility, appetite, and food intake [5]. GIP, however, exerts both glucagonotropic (during conditions with low plasma glucose) and glucagon-neutral (during conditions with high plasma glucose) effects [6]. Both GLP-1 and GIP are metabolized rapidly by the ubiquitous enzyme dipeptidyl peptidase 4 (DPP-4), which truncates the N-terminal ends, whereby the biological activity of both hormones as for insulin secretion is abolished [5].