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Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.

Authors: Asahara, S  Shibutani, Y  Teruyama, K  Inoue, H Y  Kawada, Y  Etoh, H  Matsuda, T  Kimura-Koyanagi, M  Hashimoto, N  Sakahara, M  Fujimoto, W  Takahashi, H  Ueda, S  Hosooka, T  Satoh, T  Inoue, H  Matsumoto, M  Aiba, A  Kasuga, M  Kido, Y 
Citation: Asahara S, etal., Diabetologia. 2013 May;56(5):1088-97. doi: 10.1007/s00125-013-2849-5. Epub 2013 Feb 15.
Pubmed: (View Article at PubMed) PMID:23412604
DOI: Full-text: DOI:10.1007/s00125-013-2849-5

AIMS/HYPOTHESIS: 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/INTERPRETATION: In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.


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CRRD Object Information
CRRD ID: 14392803
Created: 2019-03-01
Species: All species
Last Modified: 2019-03-01
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.