What if Gut Hormones Aren't Really Hormones: DPP-4 Inhibition and Local Action of GLP-1 in the Gastrointestinal Tract

Abstract

It is increasingly clear that the gastrointestinal (GI) tract plays a major role in glucose regulation after meal ingestion. A prominent mechanism of GI influence over blood glucose is through the secretion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1), together termed incretins because of their actions to stimulate internal secretions (i.e., insulin). Indeed, common estimates are that 70% of β-cell release after meals is attributable to the incretins, and both of these peptides are necessary for normal glucose tolerance (1). Moreover, iv administration of GLP-1, and to a much lesser degree glucose-dependent insulinotropic polypeptide, enhances insulin secretion and improves glucose disposal in persons with type 2 diabetes. This has led to the development of two new classes of medication for diabetes, GLP-1 receptor agonists, which mimic the effects of endogenous GLP-1, and dipeptidyl peptidase IV (DPP-4) inhibitors, which prevent metabolism of the native peptide and extend its activity (2).