Co-expression and regulation of connexins 36 and 43 in cultured neonatal rat pancreatic islets

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Abstract:

Fetal and neonatal pancreatic islets present a lower insulin secretory response as compared with adult islets. Prolonged culturing leads to an improvement of the glucose-induced insulin secretion response in neonatal pancreatic islets that may involve regulation of gap junction mediated cell communication. In this study, we investigated the effect of culturing neonatal islet cells for varying periods of time and with different glucose medium concentrations on the cellular expression of the endocrine pancreatic gap junction associated connexin (Cx) 36 and Cx43. We report here that the 7-d culture induced upregulation of the expression of these junctional proteins in neonatal islets in a time-dependent manner. A correlation was observed between the increased mRNA and protein expression of Cx36 and Cx43 and the increased insulin secretion following islet culturing. In addition, increasing glucose concentration within the culture medium induced a concentration-dependent enhancement of Cx36 islet expression, but not of Cx43 expression in cultured neonatal islets. In conclusion, we suggest that the regulation of gap junctional proteins by culture medium containing factors and glucose may be an important event for the maturation process of  cells observed at in vitro conditions.Key words: connexin 36, connexin 43, gap junctions, insulin secretion, in vitro maturation, neonatal pancreatic islets.

Les îlots pancréatiques fœtaux et néonatals ont une réponse insulino-sécrétoire plus faible que les îlots adultes. Une mise en culture prolongée améliore la sécrétion d'insuline induite par le glucose dans les îlots néonatals, ce qui pourrait impliquer la régulation de la communication intercellulaire par les jonctions lacunaires. Dans la présente étude, nous avons examiné l'effet de la mise en culture de cellules insulaires néonatales, à diverses périodes et avec différentes concentrations de glucose, sur l'expression des protéines Cx36 et Cx43 associées aux jonctions lacunaires endocrines pancréatiques. Nous montrons qu'une culture de 7 jours augmente l'expression de ces protéines jonctionnelles en fonction du temps dans les îlots néonatals. Nous avons observé une corrélation entre l'augmentation de l'expres sion de des protéines Cx36 et Cx43 et de leur ARNm et une augmentation de la sécrétion d'insuline après la mise en culture des îlots. De plus, l'augmentation de la concentration de glucose dans le milieu de culture a induit une augmentation concentration dépendante de l'expression de Cx36, mais pas de Cx43, dans les îlots néonatals. En conclusion, nous suggérons que la régulation des protéines des jonctions lacunaires par un milieu de culture contenant des facteurs et du glucose pourrait être une phase importante de la maturation in vitro des cellules .Mots clés : connexine 36, connexine 43, jonctions lacunaires, sécrétion d'insuline, maturation in vitro, îlots pancréatiques néonatals.[Traduit par la Rédaction]

Document Type: Research Article

Publication date: February 1, 2005

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