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Title: Kinin B1 Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity
Authors: Mori, Marcelo A. [UNIFESP]
Sales, Vicencia Micheline [UNIFESP]
Motta, Fabiana Louise [UNIFESP]
Fonseca, Raphael Gomes [UNIFESP]
Alenina, Natalia
Guadagnini, Dioze
Schadock, Ines
Silva, Elton Dias [UNIFESP]
Torres, Hugo Arruda de Moura [UNIFESP]
Santos, Edson Lucas dos [UNIFESP]
Castro, Charlles Heldan [UNIFESP]
D'Almeida, Vania [UNIFESP]
Andreotti, Sandra
Campana, Amanda Baron
Sertie, Rogerio A. L.
Saad, Mario J. A.
Lima, Fabio Bessa
Bader, Michael
Pesquero, João Bosco [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Max Delbruck Ctr Mol Med MDC
Universidade Estadual de Campinas (UNICAMP)
Universidade de São Paulo (USP)
Issue Date: 14-Sep-2012
Publisher: Public Library Science
Citation: Plos One. San Francisco: Public Library Science, v. 7, n. 9, 11 p., 2012.
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.
ISSN: 1932-6203
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