HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kowluru, A. Articles by Veluthakal, R. Search for Related Content PubMed PubMed Citation Articles by Kowluru, A. Articles by Veluthakal, R. Social Bookmarking                What's this?

Rho Guanosine Diphosphate–Dissociation Inhibitor Plays a Negative Modulatory Role in Glucose-Stimulated Insulin Secretion

From the Department of Pharmaceutical Sciences, Wayne State University and ß-Cell Biochemistry Research Laboratory, John D. Dingell VA Medical Center, Detroit, Michigan

Extant studies have implicated the Rho subfamily of guanosine triphosphate–binding proteins (G-proteins; e.g., Rac1) in physiological insulin secretion from isolated ß-cells. However, very little is known with regard to potential regulation by G-protein regulatory factors (e.g., the guanosine diphosphate–dissociation inhibitor [GDI]) of insulin secretion from the islet ß-cell. To this end, using Triton X-114 phase partition, co-immunoprecipitation, and sucrose density gradient centrifugation approaches, we report coexistence of GDI with Rac1 in insulin-secreting ß-cells (INS cells). Overexpression of wild-type GDI significantly inhibited glucose-induced, but not KCl- or mastoparan-induced, insulin secretion from INS cells. Furthermore, glucose-stimulated insulin secretion (GSIS) was significantly increased in INS cells in which expression of GDI was inhibited via the small interfering RNA–mediated knockdown approach. Together, these data appear to suggest an inhibitory role for GDI in the glucose metabolic signaling cascade, which may be relevant for GSIS.

Abbreviations: ARF6, ADP-ribosylation factor 6; GDI, guanosine diphosphate–dissociation inhibitor; GDP, guanosine diphosphate; G-protein, guanosine triphosphate–binding protein; GSIS, glucose-stimulated insulin secretion; GTP, guanosine triphosphate; Mas, mastoparan; PIP₂, phosphatidylinositol 4,5-bisphosphate; RGF, G-protein regulatory factor; RhoGDI, Rho guanosine diphosphate–dissociation inhibitor; siRNA, small interfering RNA

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Fu, M. M. Sabra, C. Damcott, T. I. Pollin, L. Ma, S. Ott, J. C. Shelton, X. Shi, L. Reinhart, J. O'Connell, et al. Evidence That Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) on 1q21 is a Type 2 Diabetes Susceptibility Gene in the Old Order Amish Diabetes, May 1, 2007; 56(5): 1363 - 1368. [Abstract] [Full Text] [PDF]

				Z. Wang, E. Oh, and D. C. Thurmond Glucose-stimulated Cdc42 Signaling Is Essential for the Second Phase of Insulin Secretion J. Biol. Chem., March 30, 2007; 282(13): 9536 - 9546. [Abstract] [Full Text] [PDF]

				P. McDonald, R. Veluthakal, H. Kaur, and A. Kowluru Biologically active lipids promote trafficking and membrane association of Rac1 in insulin-secreting INS 832/13 cells Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1216 - C1220. [Abstract] [Full Text] [PDF]

				R. Veluthakal, H. Kaur, M. Goalstone, and A. Kowluru Dominant-Negative {alpha}-Subunit of Farnesyl- and Geranyltransferase Inhibits Glucose-Stimulated, but Not KCl-Stimulated, Insulin Secretion in INS 832/13 Cells Diabetes, January 1, 2007; 56(1): 204 - 210. [Abstract] [Full Text] [PDF]