Fundação 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)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.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.3031E144E151Fundação 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 Foundation [310030_141162, CR32I3_129987]Juvenile Diabetes Research Foundation [40-2011-11]European Union [BETAIMAGE 222980, IMI, IMIDIA, C2008-T7]Fundação 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)FAPESP [2006/50758-3, 2009/52824-1, 2010/50789-1]CNPq [201862/207-7]Swiss National Science Foundation [310030_141162, CR32I3_129987]Juvenile Diabetes Research Foundation [40-2011-11]European Union [BETAIMAGE 222980, IMI, IMIDIA, C2008-T7]