Junctional communication of pancreatic β cells contributes to the control of insulin secretion and glucose tolerance

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Abstract

Proper insulin secretion requires the coordinated functioning of the numerous β cells that form pancreatic islets. This coordination depends on a network of communication mechanisms whereby β cells interact with extracellular signals and adjacent cells via connexin channels. To assess whether connexin-dependent communication plays a role in vivo, we have developed transgenic mice in which connexin 32 (Cx32), one of the vertebrate connexins found in the pancreas, is expressed in β cells. We show that the altered β-cell coupling that results from this expression causes reduced insulin secretion in response to physiologically relevant concentrations of glucose and abnormal tolerance to the sugar. These alterations were observed in spite of normal numbers of islets, increased insulin content, and preserved secretory response to glucose by individual β cells. Moreover, glucose-stimulated islets showed improved electrical synchronization of these cells and increased cytosolic levels of Ca2+. The results show that connexins contribute to the control of β cells in vivo and that their excess is detrimental for insulin secretion.

Authors

Anne Charollais, Asllan Gjinovci, Joachim Huarte, Juliette Bauquis, Angel Nadal, Franz Martín, Etelvina Andreu, Juan V. Sánchez-Andrés, Alessandra Calabrese, Domenico Bosco, Bernat Soria, Claes B. Wollheim, Pedro L. Herrera, Paolo Meda