Helmholtz Gemeinschaft


Kinin b(1) receptor in adipocytes regulates glucose tolerance and predisposition to obesity

[img] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Item Type:Article
Title:Kinin b(1) receptor in adipocytes regulates glucose tolerance and predisposition to obesity
Creators Name:Mori, M.A. and Sales, V.M. and Motta, F.L. and Fonseca, R.G. and Alenina, N. and Guadagnini, D. and Schadock, I. and Silva, E.D. and Torres, H.A. and Dos Santos, E.L. and Castro, C.H. and D'Almeida, V. and Andreotti, S. and Campana, A.B. and Sertie, R.A. and Saad, M.J. and Lima, F.B. and Bader, M. and Pesquero, J.B.
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 B(1) 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.
Keywords:Adipocytes, Bradykinin B1 Receptor, Gene Expression Regulation, Genetic Predisposition to Disease, Glucose, Glucose Transporter Type 4, Insulin, Insulin Resistance, Kinins, Knockout Mice, Obesity, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e44782
Date:14 September 2012
Official Publication:https://doi.org/10.1371/journal.pone.0044782
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library