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Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity

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) receptor...

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Autores principales: Mori, Marcelo A., Sales, Vicência Micheline, Motta, Fabiana Louise, Fonseca, Raphael Gomes, Alenina, Natalia, Guadagnini, Dioze, Schadock, Ines, Silva, Elton Dias, Torres, Hugo A. M., dos Santos, Edson Lucas, Castro, Charlles Heldan, D’Almeida, Vânia, Andreotti, Sandra, Campaña, Amanda Baron, Sertié, Rogério A. L., Saad, Mario J. A., Lima, Fabio Bessa, Bader, Michael, Pesquero, João Bosco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443087/
https://www.ncbi.nlm.nih.gov/pubmed/23024762
http://dx.doi.org/10.1371/journal.pone.0044782
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author Mori, Marcelo A.
Sales, Vicência Micheline
Motta, Fabiana Louise
Fonseca, Raphael Gomes
Alenina, Natalia
Guadagnini, Dioze
Schadock, Ines
Silva, Elton Dias
Torres, Hugo A. M.
dos Santos, Edson Lucas
Castro, Charlles Heldan
D’Almeida, Vânia
Andreotti, Sandra
Campaña, Amanda Baron
Sertié, Rogério A. L.
Saad, Mario J. A.
Lima, Fabio Bessa
Bader, Michael
Pesquero, João Bosco
author_facet Mori, Marcelo A.
Sales, Vicência Micheline
Motta, Fabiana Louise
Fonseca, Raphael Gomes
Alenina, Natalia
Guadagnini, Dioze
Schadock, Ines
Silva, Elton Dias
Torres, Hugo A. M.
dos Santos, Edson Lucas
Castro, Charlles Heldan
D’Almeida, Vânia
Andreotti, Sandra
Campaña, Amanda Baron
Sertié, Rogério A. L.
Saad, Mario J. A.
Lima, Fabio Bessa
Bader, Michael
Pesquero, João Bosco
author_sort Mori, Marcelo A.
collection PubMed
description 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.
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spelling pubmed-34430872012-09-28 Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity Mori, Marcelo A. Sales, Vicência Micheline Motta, Fabiana Louise Fonseca, Raphael Gomes Alenina, Natalia Guadagnini, Dioze Schadock, Ines Silva, Elton Dias Torres, Hugo A. M. dos Santos, Edson Lucas Castro, Charlles Heldan D’Almeida, Vânia Andreotti, Sandra Campaña, Amanda Baron Sertié, Rogério A. L. Saad, Mario J. A. Lima, Fabio Bessa Bader, Michael Pesquero, João Bosco PLoS One Research Article 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. Public Library of Science 2012-09-14 /pmc/articles/PMC3443087/ /pubmed/23024762 http://dx.doi.org/10.1371/journal.pone.0044782 Text en © 2012 Mori et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mori, Marcelo A.
Sales, Vicência Micheline
Motta, Fabiana Louise
Fonseca, Raphael Gomes
Alenina, Natalia
Guadagnini, Dioze
Schadock, Ines
Silva, Elton Dias
Torres, Hugo A. M.
dos Santos, Edson Lucas
Castro, Charlles Heldan
D’Almeida, Vânia
Andreotti, Sandra
Campaña, Amanda Baron
Sertié, Rogério A. L.
Saad, Mario J. A.
Lima, Fabio Bessa
Bader, Michael
Pesquero, João Bosco
Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity
title Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity
title_full Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity
title_fullStr Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity
title_full_unstemmed Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity
title_short Kinin B(1) Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity
title_sort kinin b(1) receptor in adipocytes regulates glucose tolerance and predisposition to obesity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443087/
https://www.ncbi.nlm.nih.gov/pubmed/23024762
http://dx.doi.org/10.1371/journal.pone.0044782
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