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

Proper insulin secretion requires the coordinated functioning of the numero us beta cells that form pancreatic islets. This coordination depends on a n etwork of communication mechanisms whereby beta cells interact with extrace llular signals and adjacent cells via connexin channels. To assess whether connexin-dependent communication plays a role in vivo, we have developed tr ansgenic mice in which connexin 32 (Cx32), one of the vertebrate connexins found in the pancreas, is expressed in beta cells. We show that the altered beta-cell coupling that results from this expression causes reduced insuli n secretion in response to physiologically relevant concentrations of gluco se 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 beta cells. Moreover, glucose- stimulated islets showed improved electrical synchronization of these cells and increased cytosolic levels of Ca2+. The results show that connexins co ntribute to the control of beta cells in vivo and that their excess is detr imental for insulin secretion.