Affiliation:
1. From the Department of Pharmaceutical Sciences, Wayne State University and β-Cell Biochemistry Research Laboratory, John D. Dingell VA Medical Center, Detroit, Michigan
Abstract
Extant studies have implicated the Rho subfamily of guanosine triphosphate–binding proteins (G-proteins; e.g., Rac1) in physiological insulin secretion from isolated β-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 β-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 β-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.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
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