title: Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.
abstract: OBJECTIVE
  The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function.
  
  
  METHODS
  Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells.
  
  
  RESULTS
  BetaRac1(-/-) mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1(-/-) mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion.
  
  
  CONCLUSIONS
  In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.
authors: Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: S
authors: S
authors: Asahara
authors: Y
authors: Y
authors: Shibutani
authors: K
authors: K
authors: Teruyama
authors: H Y
authors: HY
authors: Inoue
authors: Y
authors: Y
authors: Kawada
authors: H
authors: H
authors: Etoh
authors: T
authors: T
authors: Matsuda
authors: M
authors: M
authors: Kimura-Koyanagi
authors: N
authors: N
authors: Hashimoto
authors: M
authors: M
authors: Sakahara
authors: W
authors: W
authors: Fujimoto
authors: H
authors: H
authors: Takahashi
authors: S
authors: S
authors: Ueda
authors: T
authors: T
authors: Hosooka
authors: T
authors: T
authors: Satoh
authors: H
authors: H
authors: Inoue
authors: M
authors: M
authors: Matsumoto
authors: A
authors: A
authors: Aiba
authors: M
authors: M
authors: Kasuga
authors: Y
authors: Y
authors: Kido
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010477:Perfusion; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D055571:Secretory Pathway; D046509:Tissue Culture Techniques; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D009479:Neuropeptides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein