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Diabetologia
Published in: Diabetologia 5/2013

Open Access 01-05-2013 | Article

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

Authors: S. Asahara, Y. Shibutani, K. Teruyama, H. Y. Inoue, Y. Kawada, H. Etoh, T. Matsuda, M. Kimura-Koyanagi, N. Hashimoto, M. Sakahara, W. Fujimoto, H. Takahashi, S. Ueda, T. Hosooka, T. Satoh, H. Inoue, M. Matsumoto, A. Aiba, M. Kasuga, Y. Kido

Published in: Diabetologia | Issue 5/2013

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Abstract

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.
Appendix
Available only for authorised users
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Metadata
Title
Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin
Authors
S. Asahara
Y. Shibutani
K. Teruyama
H. Y. Inoue
Y. Kawada
H. Etoh
T. Matsuda
M. Kimura-Koyanagi
N. Hashimoto
M. Sakahara
W. Fujimoto
H. Takahashi
S. Ueda
T. Hosooka
T. Satoh
H. Inoue
M. Matsumoto
A. Aiba
M. Kasuga
Y. Kido
Publication date
01-05-2013
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 5/2013
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-2849-5

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