Species-Specific Actions of Incretin: From the Evolutionary Perspective

Yukiko Kawasaki1, Yoshiyuki Hamamoto1 and Hiroyuki Koshiyama1,21Center for Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, Osaka Japan. 2Graduate School of Medicine, Kyoto University, Kyoto, Japan.AbstractTwo modes of incretin-based therapy, incretin mimetics (ie, glucagon-like peptide-1 (GLP-1) agonists) and incretin enhancers (ie, inhibitors of dipeptidyl peptidase IV (DPP-IV)), have recently been introduced into the clinical use. From the viewpoint of evolutionary endocrinology of GLP-1 and their receptors, the incretin action of GLP-1 seems to be relatively recent. Exendin-3 and exendin-4 are paralogs of GLP-1 from the lizards, and the synthetic exendin-4, exenatide, is a paralog of GLP-1. It has recently been indicated that GLP-1 and its receptor are expressed in the taste buds of the tongue, suggesting their possible function in the taste sensing signal pathway. In order to elucidate unknown functions of GLP-1 and its agonists and enhancers, ie, other than incretin actions in humans, it is possibly useful to consider GLP-1 from the viewpoint of integrated systems biology and evolutionary endocrinology.