title: Study of the potential association of adipose tissue GLP-1 receptor with obesity and insulin resistance.
abstract: The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on β-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R) in AT and obesity and insulin resistance (IR). We provide evidence for the presence of this receptor in AT and show that its mRNA and protein expressions are increased in visceral adipose depots from morbidly obese patients with a high degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in 3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP-1R in AT correlated positively with the homeostasis model assessment index in obese IR subjects. Furthermore, prospective studies carried out with patients that underwent biliopancreatic diversion surgery showed that subjects with high levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this tissue, were those whose insulin sensitivity improved after surgery, suggesting the potential relationship between AT GLP-1R and insulin sensitivity amelioration in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system in AT represents another potential candidate for improving insulin sensitivity in obese patients.
authors.affiliation: University Hospital of Tarragona Joan XXIII, IISPV, Rovira i Virgili University, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, 43007 Tarragona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: Rajaa
authors.initials: R
authors.lastname: El Bekay
authors.forename: Belén
authors.initials: B
authors.lastname: Peral
authors.forename: Eduardo
authors.initials: E
authors.lastname: García-Fuentes
authors.forename: Anna
authors.initials: A
authors.lastname: Megia
authors.forename: Manuel
authors.initials: M
authors.lastname: Macias-Gonzalez
authors.forename: José
authors.initials: J
authors.lastname: Fernández Real
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Jimenez-Gomez
authors.forename: Xavier
authors.initials: X
authors.lastname: Escoté
authors.forename: Gisela
authors.initials: G
authors.lastname: Pachón
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
authors.forename: David M
authors.initials: DM
authors.lastname: Selva
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Tinahones
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D011446:Prospective Studies; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1