Connexins and ß-cell functions.

Proper functioning of pancreatic islets requires that numerous ß-cells are properly coordinated. With evolution, many mechanisms have converged, which now allow individual ß-cells to sense the state of activity of their neighbors as well as the changes taking place in the extracellular medium, and to regulate accordingly their own function. Here, we review one such mechanism for intercellular coordination, which depends on connexins. These integral membrane proteins accumulate at sites of close apposition between adjacent islet cell membranes, referred to as gap junctions. Recent evidence demonstrates that connexin-dependent signaling is relevant for the in vivo control of insulin biosynthesis and release, as well as for the survival of ß-cells under stressing conditions. The data suggest that alterations of this signaling may be implicated in the ß-cell alterations which characterize most forms of diabetes, raising the tantalizing possibility that targeting of the direct intercellular communications ß-cells establish within each pancreatic islet may provide a novel, therapeutically useful strategy.