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.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Vendrell J,El Bekay R,Peral B,García-Fuentes E,Megia A,Macias-Gonzalez M,Fernández Real J,Jimenez-Gomez Y,Escoté X,Pachón G,Simó R,Selva DM,Malagón MM,Tinahones FJ

doi

10.1210/en.2011-1070

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

4072-9

issue

11

eissn

0013-7227

issn

1945-7170

pii

en.2011-1070

journal_volume

152

pub_type

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