Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice

Detalhes bibliográficos
Autor(a) principal: Carvalho, Carolina Prado de França [UNIFESP]
Data de Publicação: 2012
Outros Autores: Oliveira, R. B., Britan, A., Santos-Silva, J. C., Boschero, A. C., Meda, P., Collares-Buzato, C. B.
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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spelling 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