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

被引：87

作者：

Asahara, S. ^{[1
]}

Shibutani, Y. ^{[1
]}

Teruyama, K. ^{[2
]}

Inoue, H. Y. ^{[2
]}

Kawada, Y. ^{[2
]}

Etoh, H. ^{[2
]}

Matsuda, T. ^{[1
]}

Kimura-Koyanagi, M. ^{[1
]}

Hashimoto, N. ^{[1
]}

Sakahara, M. ^{[3
]}

Fujimoto, W. ^{[4
]}

Takahashi, H. ^{[4
]}

Ueda, S. ^{[5
]}

Hosooka, T. ^{[1
]}

Satoh, T. ^{[6
]}

Inoue, H. ^{[7
]}

Matsumoto, M. ^{[8
]}

Aiba, A. ^{[9
]}

Kasuga, M. ^{[8
]}

Kido, Y. ^{[1
,2
]}

机构：

[1] Kobe Univ, Div Diabet & Endocrinol, Grad Sch Med, Kobe, Hyogo 6540142, Japan

[2] Kobe Univ, Grad Sch Hlth Sci, Div Med Chem, Kobe, Hyogo 6540142, Japan

[3] Japanese Fdn Canc Res, Inst Canc, Tokyo 170, Japan

[4] Kobe Univ, Div Cellular & Mol Med, Grad Sch Med, Kobe, Hyogo 6540142, Japan

[5] Kobe Univ, Grad Sch Agr Sci, Kobe, Hyogo 6540142, Japan

[6] Kobe Univ, Grad Sch Med, Div Mol Biol, Kobe, Hyogo 6540142, Japan

[7] Kanazawa Univ, Dept Physiol & Metab, Brain Liver Interface Med Res Ctr, Coll Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa, Japan

[8] Natl Ctr Global Hlth & Med, Res Inst, Tokyo, Japan

[9] Univ Tokyo, Fac Med, Lab Anim Resources, Ctr Dis Biol & Integrat Med, Tokyo 113, Japan

来源：

DIABETOLOGIA | 2013年 / 56卷 / 05期

关键词：

Beta cell; Diabetes; F-actin; Insulin secretion; RAC1; PANCREATIC BETA-CELLS; GLUCAGON-LIKE PEPTIDE-1; GRANULE EXOCYTOSIS; PKC-LAMBDA; IN-VIVO; ACTIVATION; EXPRESSION; RECEPTOR; DYNAMICS; MICE;

D O I：

10.1007/s00125-013-2849-5

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：1088 / 1097

页数：10

共 45 条

[1]

Stem cell depletion through epidermal deletion of Rac1 [J].