title: 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.
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cantini
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Franco
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy; Diabetes Agency, Careggi Hospital, Florence, Italy. Electronic address: edoardo.mannucci@unifi.it.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Endocrinology Unit, University of Florence, Florence, Italy. Electronic address: michaela.luconi@unifi.it.
authors.forename: Michaela
authors.initials: M
authors.lastname: Luconi
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D010455:Peptides / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D052242:Adiponectin; D010455:Peptides; C114437:glucagon-like peptide-1 (9-36)-amide; D052216:Glucagon-Like Peptide 1
keywords: Adipose stem cells; Alternative GLP-1R; Dipeptidyl peptidase-4 inhibitors; Glucagon-like peptide-1