Is cleaved glucagon-like peptide 1 really inactive? Effects of GLP-1(9-36) on human adipose stem cells

Abstract

Glucagon-like peptide 1(9-36) [GLP-1(9-36)] is generated by dipeptidyl peptidase-4 (DPP4) cleavage of the gut incretin hormone, GLP-1(7-36). Since GLP-1(9-36) has a very low affinity for the GLP-1 receptor (GLP-1R), it has so far been considered an inactive form of GLP-1. Here we show GLP-1(9-36) activity in human adipose stem cells (ASC) in vitro. GLP-1(9-36) inhibits human ASC proliferation, glucose uptake and adipogenesis, as well as induces cell apoptosis, to a similar extent as GLP-1(7-36) and liraglutide. Since GLP-1(9-36) effects are not reverted by the receptor antagonist exendin(9-39), which conversely reverts the effects of GLP-1(7-36), we hypothesized that the former may be mediated by a GLP-1 receptor different from the classical pancreatic one. This is the first report of GLP-1(9-36) activity in human adipose cells. Nevertheless, these findings deserve further preclinical studies to better elucidate novel and unforeseen GLP-1(9-36) activities, which could allow a better understanding of the clinical profile of DPP4 inhibitors and GLP-1R agonists.

Keywords: Adipose stem cells; Alternative GLP-1R; Dipeptidyl peptidase-4 inhibitors; Glucagon-like peptide-1.