Constitutive activation of Rac1 in pancreatic β cells facilitates F-actin depolymerization but exerts no influence on the increase of pancreatic β cell mass and facilitation of insulin secretion.

Insulin secretion from pancreatic β cells has an important role in the onset of type 2 diabetes. Insulin secretion from pancreatic β cells is regulated by pancreatic β cell mass and their insulin secretory function. By using pancreatic β cell-specific Rac1-knockout mice, we recently showed that Rac1 deletion, even with no reduction in pancreatic β cell mass, inhibits F-actin depolymerization, which causes insulin secretion to decline. However, the effect of Rac1 deficiency on the growth and apoptosis of pancreatic β cells was not clarified. Further, the effect of constitutive Rac1 activation on the secretion of insulin from pancreatic β cells has not been studied. Here, we used pancreatic islets isolated from pancreatic β cell-specific Rac1-knockout mice to evaluate the growth and apoptosis of pancreatic β cells. We found that Rac1 deficiency does not influence the growth or apoptosis of pancreatic β cells. Further, when a constitutively activated form of Rac1 (G12V) is expressed, F-actin depolymerization was increased in the pancreatic β cell lines, which had no effect on pancreatic β cell growth or glucose-stimulated insulin secretion. These findings indicate that excessive Rac1 expression or activation in pancreatic β cells facilitates F-actin depolymerization, but has no effect on insulin secretion.