Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0040573 http://hdl.handle.net/11449/42446 |
Resumo: | The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM. |
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Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor GenesThe Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed São Paulo, Dept Biophys, São Paulo, BrazilMax Delbruck Ctr Mol Med, Berlin, GermanyUniv Estadual Campinas, Campinas, SP, BrazilUniv Estadual Paulista, São Paulo, BrazilUniv São Paulo, Sch Arts Sci & Humanities, São Paulo, BrazilUniv Fed São Paulo, Dept Sci & Technol, Sao Jose Dos Campos, BrazilUniv Fed São Paulo, Dept Pathol, São Paulo, BrazilUniv Estadual Paulista, São Paulo, BrazilPublic Library ScienceUniversidade Federal de São Paulo (UNIFESP)Max Delbruck Ctr Mol MedUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Barros, Carlos C.Haro, AndersonRusso, Fernanda J. V. P.Schadock, InesAlmeida, Sandro S.Ribeiro, Rosane A.Vanzela, Emerielle C.Lanzoni, Valeria P.Barros, Flavio C. [UNESP]Moraes, Milton R.Mori, Marcelo A.Bacurau, Reury F. P.Wurtele, MartinBoschero, Antonio C.Carneiro, Everardo M.Bader, MichaelPesquero, Joao B.Araujo, Ronaldo C.2014-05-20T15:34:10Z2014-05-20T15:34:10Z2012-07-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://dx.doi.org/10.1371/journal.pone.0040573Plos One. San Francisco: Public Library Science, v. 7, n. 7, p. 11, 2012.1932-6203http://hdl.handle.net/11449/4244610.1371/journal.pone.0040573WOS:000306956300015WOS000306956300015.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLOS ONE2.7661,164info:eu-repo/semantics/openAccess2024-01-11T06:25:07Zoai:repositorio.unesp.br:11449/42446Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-11T06:25:07Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes |
title |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes |
spellingShingle |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes Barros, Carlos C. |
title_short |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes |
title_full |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes |
title_fullStr |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes |
title_full_unstemmed |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes |
title_sort |
Altered Glucose Homeostasis and Hepatic Function in Obese Mice Deficient for Both Kinin Receptor Genes |
author |
Barros, Carlos C. |
author_facet |
Barros, Carlos C. Haro, Anderson Russo, Fernanda J. V. P. Schadock, Ines Almeida, Sandro S. Ribeiro, Rosane A. Vanzela, Emerielle C. Lanzoni, Valeria P. Barros, Flavio C. [UNESP] Moraes, Milton R. Mori, Marcelo A. Bacurau, Reury F. P. Wurtele, Martin Boschero, Antonio C. Carneiro, Everardo M. Bader, Michael Pesquero, Joao B. Araujo, Ronaldo C. |
author_role |
author |
author2 |
Haro, Anderson Russo, Fernanda J. V. P. Schadock, Ines Almeida, Sandro S. Ribeiro, Rosane A. Vanzela, Emerielle C. Lanzoni, Valeria P. Barros, Flavio C. [UNESP] Moraes, Milton R. Mori, Marcelo A. Bacurau, Reury F. P. Wurtele, Martin Boschero, Antonio C. Carneiro, Everardo M. Bader, Michael Pesquero, Joao B. Araujo, Ronaldo C. |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Max Delbruck Ctr Mol Med Universidade Estadual de Campinas (UNICAMP) Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Barros, Carlos C. Haro, Anderson Russo, Fernanda J. V. P. Schadock, Ines Almeida, Sandro S. Ribeiro, Rosane A. Vanzela, Emerielle C. Lanzoni, Valeria P. Barros, Flavio C. [UNESP] Moraes, Milton R. Mori, Marcelo A. Bacurau, Reury F. P. Wurtele, Martin Boschero, Antonio C. Carneiro, Everardo M. Bader, Michael Pesquero, Joao B. Araujo, Ronaldo C. |
description |
The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-07-19 2014-05-20T15:34:10Z 2014-05-20T15:34:10Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0040573 Plos One. San Francisco: Public Library Science, v. 7, n. 7, p. 11, 2012. 1932-6203 http://hdl.handle.net/11449/42446 10.1371/journal.pone.0040573 WOS:000306956300015 WOS000306956300015.pdf |
url |
http://dx.doi.org/10.1371/journal.pone.0040573 http://hdl.handle.net/11449/42446 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 7, n. 7, p. 11, 2012. 1932-6203 10.1371/journal.pone.0040573 WOS:000306956300015 WOS000306956300015.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLOS ONE 2.766 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1797790260393934848 |