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.
Is cleaved glucagon-like peptide 1 really inactive? Effects of GLP-1(9-36) on human adipose stem cells / Cantini, Giulia; DI FRANCO, Alessandra; Mannucci, Edoardo; Luconi, Michaela. - In: MOLECULAR AND CELLULAR ENDOCRINOLOGY. - ISSN 0303-7207. - STAMPA. - 439:(2017), pp. 10-15. [10.1016/j.mce.2016.10.013]
Is cleaved glucagon-like peptide 1 really inactive? Effects of GLP-1(9-36) on human adipose stem cells.
CANTINI, GIULIA;DI FRANCO, ALESSANDRA;MANNUCCI, EDOARDO;LUCONI, MICHAELA
2017
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.File | Dimensione | Formato | |
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