The In Vivo β-to-β-Cell Chat Room: Connexin Connections Matter

  1. Paolo Meda
  1. Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
  1. Corresponding author: Paolo Meda, paolo.meda{at}unige.ch.

Proper glycemic control requires that numerous β-cells are coordinated to rapidly, but temporarily, secrete insulin after meals. This coordination integrates hundreds of β-cells within each islet into a functionally homogeneous unit. This homogeneity occurs despite the intrinsic heterogeneity of individual β-cells (1). Fine-tuning of this coordination is further required because of the cyclic oscillations that ionic, metabolic, and effector events undergo within each islet, as well as among the many islets of a pancreas. Together, these events ensure normal pulsatility of insulin secretion (2,3). Many mechanisms have evolved over time to achieve this coordination (14). One such mechanism is cell-to-cell coupling, the process by which contiguous cells exchange cytosolic molecules (Fig. 1) via channels made of connexin (Cx) proteins. These proteins concentrate at gap junction domains of the cell membrane (4).

FIG. 1.

In control islets, Cx36 channels allow for the exchange of electrotonic currents and cytosolic molecules between coupled β-cells. Islets null for Cx36 no longer feature this coupling, which causes the loss of the intercellular synchronization of glucose-induced Ca2+ transients and of pulsatile insulin release, as well as an extended off-response of β-cells. These alterations are associated with a decrease in the expression of the Ins genes and in both first and second phases of GSIS, which result in impaired glucose tolerance of the Cx36-null mice. It is still unclear (?) whether loss of Cx36 also sufficiently raises the basal secretion of insulin to alter the circulating levels of the hormone. Whether similar changes also take place after the temporary uncoupling of β-cells, resulting from the closure of Cx36 channels, is still largely undetermined (nd). Many aspects of β-cell function also remain to be investigated in …

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