Rhes expression in pancreatic β-cells is regulated by efaroxan in a calcium-dependent process

The monomeric G-protein Rhes has been described to be present in pancreatic β-cells, and a putative role in the control of insulin release has been proposed. Here, we show that treatment of β-cells with the imidazoline insulin secretagogue efaroxan resulted in a concentration- and time-dependent increase in the expression of Rhes, which peaked after 4 h of efaroxan exposure; thereafter, Rhes mRNA levels decreased. Marked stereoselectivity was displayed, with (−)-efaroxan (the selectively insulinotropic enantiomer) being much more effective than (+)-efaroxan at raising Rhes transcript levels. The mechanism by which Rhes gene expression is activated in β-cells appears to require the influx of extracellular calcium and de novo protein synthesis, and is not directly associated with the release of insulin. The present results confirm our earlier proposal that Rhes is an imidazoline-regulated transcript in pancreatic β-cells. Studies to understand the role of Rhes as a regulator of β-cell function are, thus, warranted.