title: 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.
abstract: 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.
authors.affiliation: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shibutani
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Asahara
authors.forename: Kyoko
authors.initials: K
authors.lastname: Teruyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsuda
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kido
mesh_terms: D000199:Actins / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000502:physiology*; D058105:Polymerization; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
chemical_list: D000199:Actins; D007328:Insulin; D009479:Neuropeptides; D018809:Proliferating Cell Nuclear Antigen; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein