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-Cells
1 Cardiovascular Research Institute, National University Medical Institutes, National University of Singapore, Singapore, Singapore
2 Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA
* To whom correspondence should be addressed. E-mail: nmiligd{at}nus.edu.sg.
Stimulation of insulin secretion by glucose and other secretagogues from pancreatic islet 
cells is mediated by multiple signaling pathways. Rac1 is a member of Rho family GTPases
regulating cytoskeletal organization, and recent evidence also implicates Rac1 in exocytotic
process. Herein, we report that exposure of insulin-secreting INS cells to stimulatory glucose
concentrations caused translocation of Rac1 from cytosol to the membrane fraction
(including the plasmalemma), an indication of Rac1 activation. Furthermore, glucose
stimulation increased Rac1 GTPase activity. Time course study indicates that such an effect
is demonstrable only after 15 min stimulation with glucose. Expression of a dominant-negative
Rac1 mutant (N17Rac1) abolished glucose-induced translocation of Rac1, and
significantly inhibited insulin secretion stimulated by glucose and forskolin. This inhibitory
effect on glucose-stimulated insulin secretion was more apparent in the late phase of
secretion. However, N17Rac1 expression did not significantly affect insulin secretion
induced by high K+. INS-1 cells expressing N17Rac1 also displayed significant
morphological changes and disappearance of F-actin structures. Expression of wild type Rac1
or a constitutively-active Rac1 mutant (V12Rac1) did not significantly affect either the
stimulated insulin secretion or basal release, suggesting that Rac1 activation is essential, but
not sufficient, for evoking secretory process. These data suggest, for the first time, that Rac1
may be involved in glucose and forskolin stimulated insulin secretion, possibly at the level of
recruitment of secretory granules through actin cytoskeletal network reorganization.
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Y. Bi and J. A. Williams A role for Rho and Rac in secretagogue-induced amylase release by pancreatic acini Am J Physiol Cell Physiol, July 1, 2005; 289(1): C22 - C32. [Abstract] [Full Text] [PDF]
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