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Cell-to-cell contact dependence and junctional protein content are correlated with in vivo maturation of pancreatic beta cells

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In this study, we investigated the cellular distribution of junctional proteins and the dependence on cell–cell contacts of pancreatic beta cells during animal development. Fetus and newborn rat islets, which display a relatively poor insulin secretory response to glucose, present an immature morphology and cytoarchitecture when compared with young and adult islets that are responsive to glucose. At the perinatal stage, beta cells display a low junctional content of neural cell adhesion molecule (N-CAM), α- and β-catenins, ZO-1, and F-actin, while a differential distribution of N-CAM and Pan-cadherin was seen in beta cells and nonbeta cells only from young and adult islets. In the absence of intercellular contacts, the glucose-stimulated insulin secretion was completely blocked in adult beta cells, but after reaggregation they partially reestablished the secretory response to glucose. By contrast, neonatal beta cells were poorly responsive to sugar, regardless of whether they were arranged as intact islets or as isolated cells. Interestingly, after 10 days of culturing, neonatal beta cells, known to display increased junctional protein content in vitro, became responsive to glucose and concomitantly dependent on cell–cell contacts. Therefore, our data suggest that the developmental acquisition of an adult-like insulin secretory pattern is paralleled by a dependence on direct cell–cell interactions.
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Keywords: adhésion cellulaire; beta cell maturation; cell adhesion; cellules bêta du pancréas; développement du pancréas; insulin secretion; intercellular junctions; jonctions intercellulaires; junctional proteins; maturation des cellules bêta; pancreas development; pancreatic beta cells; protéines de jonction; sécrétion d’insuline

Document Type: Research Article

Affiliations: 1: Department of Histology and Embryology, Institute of Biology, University of Campinas (UNICAMP), Campinas CEP 13083-970, São Paulo, Brazil. 2: Department of Anatomy, Cell Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Publication date: July 4, 2012

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