Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice
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 UNIFESP |
dARK ID: | ark:/48912/0013000011v05 |
DOI: | 10.1152/ajpendo.00489.2011 |
Texto Completo: | https://dx.doi.org/10.1152/ajpendo.00489.2011 http://repositorio.unifesp.br/handle/11600/35022 |
Resumo: | Carvalho CP, Oliveira RB, Britan A, Santos-Silva JC, Boschero AC, Meda P, Collares-Buzato CB. Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Endocrinol Metab 303: E144-E151, 2012. First published May 8, 2012; doi: 10.1152/ajpendo.00489.2011.-Gap junctional intercellular communication between beta-cells is crucial for proper insulin biosynthesis and secretion. the aim of this work was to investigate the expression of connexin (Cx) 36 at the protein level as well as the function and structure of gap junctions (GJ) made by this protein in the endocrine pancreas of prediabetic mice. C57BL/6 mice were fed a high-fat (HF) or regular chow diet for 60 days. HF-fed mice became obese and prediabetic, as shown by peripheral insulin resistance, moderate hyperglycemia, hyperinsulinemia, and compensatory increase in endocrine pancreas mass. Compared with control mice, prediabetic animals showed a significant decrease in insulin-secretory response to glucose and displayed a significant reduction in islet Cx36 protein. Ultrastructural analysis further showed that prediabetic mice had GJ plaques about one-half the size of those of the control group. Microinjection of isolated pancreatic islets with ethidium bromide revealed that prediabetic mice featured a beta-cell-beta-cell coupling 30% lower than that of control animals. We conclude that beta-cell-beta-cell coupling mediated by Cx36 made-channels is impaired in prediabetic mice, suggesting a role of Cx36-dependent cell-to-cell communication in the pathogenesis of the early beta-cell dysfunctions that lead to type 2-diabetes. |
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Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic miceHigh-fat-fed miceType 2 diabetes mellitusConnexin 36ConnexinsCell-cell communicationInsulin secretionInsulin resistanceBeta-cell dysfunctionCarvalho CP, Oliveira RB, Britan A, Santos-Silva JC, Boschero AC, Meda P, Collares-Buzato CB. Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Endocrinol Metab 303: E144-E151, 2012. First published May 8, 2012; doi: 10.1152/ajpendo.00489.2011.-Gap junctional intercellular communication between beta-cells is crucial for proper insulin biosynthesis and secretion. the aim of this work was to investigate the expression of connexin (Cx) 36 at the protein level as well as the function and structure of gap junctions (GJ) made by this protein in the endocrine pancreas of prediabetic mice. C57BL/6 mice were fed a high-fat (HF) or regular chow diet for 60 days. HF-fed mice became obese and prediabetic, as shown by peripheral insulin resistance, moderate hyperglycemia, hyperinsulinemia, and compensatory increase in endocrine pancreas mass. Compared with control mice, prediabetic animals showed a significant decrease in insulin-secretory response to glucose and displayed a significant reduction in islet Cx36 protein. Ultrastructural analysis further showed that prediabetic mice had GJ plaques about one-half the size of those of the control group. Microinjection of isolated pancreatic islets with ethidium bromide revealed that prediabetic mice featured a beta-cell-beta-cell coupling 30% lower than that of control animals. We conclude that beta-cell-beta-cell coupling mediated by Cx36 made-channels is impaired in prediabetic mice, suggesting a role of Cx36-dependent cell-to-cell communication in the pathogenesis of the early beta-cell dysfunctions that lead to type 2-diabetes.Univ Estadual Campinas, Inst Biol, Dept Histol & Embryol, UNICAMP, BR-13083970 Campinas, SP, BrazilUniv Estadual Campinas, Inst Biol, Dept Physiol & Biophys, BR-1303970 Campinas, SP, BrazilUniv Geneva, Sch Med, Dept Cell Physiol & Metab, CH-1211 Geneva, SwitzerlandUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biosci, São Paulo, BrazilWeb of ScienceFundação 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)Swiss National Science FoundationJuvenile Diabetes Research FoundationEuropean UnionFAPESP: 2006/50758-3FAPESP: 2009/52824-1FAPESP: 2010/50789-1CNPq: 201862/207-7Swiss National Science Foundation: 310030_141162Swiss National Science Foundation: CR32I3_129987Juvenile Diabetes Research Foundation: 40-2011-11European Union: BETAIMAGE 222980European Union: IMI, IMIDIA, C2008-T7Amer Physiological SocUniversidade Estadual de Campinas (UNICAMP)Univ GenevaUniversidade Federal de São Paulo (UNIFESP)Carvalho, Carolina Prado de França [UNIFESP]Oliveira, R. B.Britan, A.Santos-Silva, J. C.Boschero, A. C.Meda, P.Collares-Buzato, C. B.2016-01-24T14:27:23Z2016-01-24T14:27:23Z2012-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionE144-E151https://dx.doi.org/10.1152/ajpendo.00489.2011American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 303, n. 1, p. E144-E151, 2012.10.1152/ajpendo.00489.20110193-1849http://repositorio.unifesp.br/handle/11600/35022WOS:000306412000013ark:/48912/0013000011v05engAmerican Journal of Physiology-endocrinology and Metabolisminfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2021-08-09T21:44:06Zoai:repositorio.unifesp.br/:11600/35022Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:50:21.653586Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice |
title |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice |
spellingShingle |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice Carvalho, Carolina Prado de França [UNIFESP] High-fat-fed mice Type 2 diabetes mellitus Connexin 36 Connexins Cell-cell communication Insulin secretion Insulin resistance Beta-cell dysfunction Carvalho, Carolina Prado de França [UNIFESP] High-fat-fed mice Type 2 diabetes mellitus Connexin 36 Connexins Cell-cell communication Insulin secretion Insulin resistance Beta-cell dysfunction |
title_short |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice |
title_full |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice |
title_fullStr |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice |
title_full_unstemmed |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice |
title_sort |
Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice |
author |
Carvalho, Carolina Prado de França [UNIFESP] |
author_facet |
Carvalho, Carolina Prado de França [UNIFESP] Carvalho, Carolina Prado de França [UNIFESP] Oliveira, R. B. Britan, A. Santos-Silva, J. C. Boschero, A. C. Meda, P. Collares-Buzato, C. B. Oliveira, R. B. Britan, A. Santos-Silva, J. C. Boschero, A. C. Meda, P. Collares-Buzato, C. B. |
author_role |
author |
author2 |
Oliveira, R. B. Britan, A. Santos-Silva, J. C. Boschero, A. C. Meda, P. Collares-Buzato, C. B. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) Univ Geneva Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Carvalho, Carolina Prado de França [UNIFESP] Oliveira, R. B. Britan, A. Santos-Silva, J. C. Boschero, A. C. Meda, P. Collares-Buzato, C. B. |
dc.subject.por.fl_str_mv |
High-fat-fed mice Type 2 diabetes mellitus Connexin 36 Connexins Cell-cell communication Insulin secretion Insulin resistance Beta-cell dysfunction |
topic |
High-fat-fed mice Type 2 diabetes mellitus Connexin 36 Connexins Cell-cell communication Insulin secretion Insulin resistance Beta-cell dysfunction |
description |
Carvalho CP, Oliveira RB, Britan A, Santos-Silva JC, Boschero AC, Meda P, Collares-Buzato CB. Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Endocrinol Metab 303: E144-E151, 2012. First published May 8, 2012; doi: 10.1152/ajpendo.00489.2011.-Gap junctional intercellular communication between beta-cells is crucial for proper insulin biosynthesis and secretion. the aim of this work was to investigate the expression of connexin (Cx) 36 at the protein level as well as the function and structure of gap junctions (GJ) made by this protein in the endocrine pancreas of prediabetic mice. C57BL/6 mice were fed a high-fat (HF) or regular chow diet for 60 days. HF-fed mice became obese and prediabetic, as shown by peripheral insulin resistance, moderate hyperglycemia, hyperinsulinemia, and compensatory increase in endocrine pancreas mass. Compared with control mice, prediabetic animals showed a significant decrease in insulin-secretory response to glucose and displayed a significant reduction in islet Cx36 protein. Ultrastructural analysis further showed that prediabetic mice had GJ plaques about one-half the size of those of the control group. Microinjection of isolated pancreatic islets with ethidium bromide revealed that prediabetic mice featured a beta-cell-beta-cell coupling 30% lower than that of control animals. We conclude that beta-cell-beta-cell coupling mediated by Cx36 made-channels is impaired in prediabetic mice, suggesting a role of Cx36-dependent cell-to-cell communication in the pathogenesis of the early beta-cell dysfunctions that lead to type 2-diabetes. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-07-01 2016-01-24T14:27:23Z 2016-01-24T14:27:23Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://dx.doi.org/10.1152/ajpendo.00489.2011 American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 303, n. 1, p. E144-E151, 2012. 10.1152/ajpendo.00489.2011 0193-1849 http://repositorio.unifesp.br/handle/11600/35022 WOS:000306412000013 |
dc.identifier.dark.fl_str_mv |
ark:/48912/0013000011v05 |
url |
https://dx.doi.org/10.1152/ajpendo.00489.2011 http://repositorio.unifesp.br/handle/11600/35022 |
identifier_str_mv |
American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 303, n. 1, p. E144-E151, 2012. 10.1152/ajpendo.00489.2011 0193-1849 WOS:000306412000013 ark:/48912/0013000011v05 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
American Journal of Physiology-endocrinology and Metabolism |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
E144-E151 |
dc.publisher.none.fl_str_mv |
Amer Physiological Soc |
publisher.none.fl_str_mv |
Amer Physiological Soc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1822251288767758336 |
dc.identifier.doi.none.fl_str_mv |
10.1152/ajpendo.00489.2011 |