title: Rho guanosine diphosphate-dissociation inhibitor plays a negative modulatory role in glucose-stimulated insulin secretion.
abstract: Extant studies have implicated the Rho subfamily of guanosine triphosphate-binding proteins (G-proteins; e.g., Rac1) in physiological insulin secretion from isolated beta-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 beta-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 beta-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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Wayne State University and Beta-Cell Biochemistry Research Laboratory, John D. Dingell VA Medical Center, Detroit, Michigan 48202, USA. akowluru@med.wayne.edu
authors.forename: Anjaneyulu
authors.initials: A
authors.lastname: Kowluru
authors.forename: Rajakrishnan
authors.initials: R
authors.lastname: Veluthakal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005947:Glucose / Q000494:pharmacology*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000502:physiology*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors; D007328:Insulin; D005947:Glucose