Evaluation of the incretin effect in humans using GIP and GLP-1 receptor antagonists

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2020-03, Vol.125, p.170183-170183, Article 170183
• Main Authors: Gasbjerg, Lærke S., Bergmann, Natasha C., Stensen, Signe, Christensen, Mikkel B., Rosenkilde, Mette M., Holst, Jens J., Nauck, Michael, Knop, Filip K.
• Format: Article
• Language: English
• Subjects: Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Evaluation Studies as Topic; Glucagon-Like Peptide-1 Receptor - therapeutic use; Humans; Incretins - therapeutic use; Insulin Secretion - drug effects; Peptide Fragments - therapeutic use; Receptors, Gastrointestinal Hormone - antagonists & inhibitors
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2019.170183

•Using incretin hormone receptor antagonists, we can distinguish GIP and GLP-1 actions•In healthy men, the incretin effect amounts to ∼60-75%•Estimated from antagonist infusions, there is a lower incretin effect of GLP-1 than GIP•Incretin hormone receptor antagonist limitations must be recognized•Endogenous GIP and GLP-1 together has not been studied in patients with T2D Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) potentiate glucose-induced insulin secretion and are therefore thought to be responsible for the incretin effect. The magnitude of the incretin effect, defined as the fraction of postprandial insulin secretion stimulated by intestinal factors, has been reported to be up to ∼60% in healthy individuals. In several pathological conditions but especially in patients with type 2 diabetes, the incretin effect is severely reduced or even absent. In line with this, the insulinotropic effects of GIP and GLP-1 are impaired in patients with type 2 diabetes, even when administered in supraphysiological doses. In healthy individuals, GIP has been proposed to be the most important incretin hormone of the two, but the individual contribution of the two is difficult to determine. However, using incretin hormone receptor antagonists: the novel GIP receptor antagonist GIP(3–30)NH2 and the widely used GLP-1 receptor antagonist exendin(9–39)NH2, we can now distinguish between the effects of the two hormones. In this review, we present and discuss studies in which the individual contribution of GIP and GLP-1 to the incretin effect in healthy individuals have been estimated and discuss the limitations of using incretin hormone receptor antagonists.