Kinin B1 Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity

Kinin B1 Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity

Author Mori, Marcelo A. Autor UNIFESP Google Scholar
Sales, Vicencia Micheline Autor UNIFESP Google Scholar
Motta, Fabiana Louise Autor UNIFESP Google Scholar
Fonseca, Raphael Gomes Autor UNIFESP Google Scholar
Alenina, Natalia Google Scholar
Guadagnini, Dioze Google Scholar
Schadock, Ines Google Scholar
Silva, Elton Dias Autor UNIFESP Google Scholar
Torres, Hugo Arruda de Moura Autor UNIFESP Google Scholar
Santos, Edson Lucas dos Autor UNIFESP Google Scholar
Castro, Charlles Heldan Autor UNIFESP Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Andreotti, Sandra Google Scholar
Campana, Amanda Baron Google Scholar
Sertie, Rogerio A. L. Google Scholar
Saad, Mario J. A. Google Scholar
Lima, Fabio Bessa Google Scholar
Bader, Michael Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Max Delbruck Ctr Mol Med MDC
Universidade Estadual de Campinas (UNICAMP)
Universidade de São Paulo (USP)
Abstract Background: Kinins participate in the pathophysiology of obesity and type 2 diabetes by mechanisms which are not fully understood. Kinin B-1 receptor knockout mice (B-1(-/-)) are leaner and exhibit improved insulin sensitivity.Methodology/Principal Findings: Here we show that kinin B-1 receptors in adipocytes play a role in controlling whole body insulin action and glucose homeostasis. Adipocytes isolated from mouse white adipose tissue (WAT) constitutively express kinin B-1 receptors. in these cells, treatment with the B-1 receptor agonist des-Arg(9)-bradykinin improved insulin signaling, GLUT4 translocation, and glucose uptake. Adipocytes from B-1(-/-) mice showed reduced GLUT4 expression and impaired glucose uptake at both basal and insulin-stimulated states. To investigate the consequences of these phenomena to whole body metabolism, we generated mice where the expression of the kinin B-1 receptor was limited to cells of the adipose tissue (aP2-B-1/B-1(-/-)). Similarly to B-1(-/-) mice, aP2-B-1/B-1(-/-) mice were leaner than wild type controls. However, exclusive expression of the kinin B1 receptor in adipose tissue completely rescued the improved systemic insulin sensitivity phenotype of B-1(-/-) mice. Adipose tissue gene expression analysis also revealed that genes involved in insulin signaling were significantly affected by the presence of the kinin B-1 receptor in adipose tissue. in agreement, GLUT4 expression and glucose uptake were increased in fat tissue of aP2-B-1/B-1(-/-) when compared to B-1(-/-) mice. When subjected to high fat diet, aP2-B-1/B-1(-/-) mice gained more weight than B-1(-/-) littermates, becoming as obese as the wild types.Conclusions/Significance: Thus, kinin B-1 receptor participates in the modulation of insulin action in adipocytes, contributing to systemic insulin sensitivity and predisposition to obesity.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Deutsche Forschungsgemeinschaft
German Ministry of Education and Science
Grant number Deutsche Forschungsgemeinschaft: BA1374/16-1
German Ministry of Education and Science: BRA09/014
Date 2012-09-14
Published in Plos One. San Francisco: Public Library Science, v. 7, n. 9, 11 p., 2012.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 11
Origin http://dx.doi.org/10.1371/journal.pone.0044782
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000308860100020
URI http://repositorio.unifesp.br/handle/11600/35272

Show full item record




File

Name: WOS000308860100020.pdf
Size: 901.7Kb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account