Paradoxical regulation of glucose-induced Rac1 activation and insulin secretion by RhoGDIβ in pancreatic β-cells. (4th March 2021)

• Record Type: Journal Article
• Authors: Thamilselvan, Vijayalakshmi; Kowluru, Anjaneyulu
• Is Part Of: Small GTPases. Volume 12:Number 2(2021)
• Page Start: 114
• Page End: 121
• Publication Date: 2021-03-04
• Subjects: RhoGDIβ -- glucose-stimulated insulin secretion -- Rac1 -- pancreatic beta-cell; Guanosine triphosphatase -- Periodicals; Guanosine triphosphatase; Periodicals; 572.793
• DOI: 10.1080/21541248.2019.1635403
• Languages: English
• ISSNs: 2154-1256

Abstract

ABSTRACT: Small GTPases (e.g., Rac1) play key roles in glucose-stimulated insulin secretion (GSIS) in the β-cell. We investigated regulation by RhoGDIβ of glucose-induced activation of Rac1 and insulin secretion. RhoGDIβ is expressed in INS-1 832/13 cells, rodent and human islets. siRNA-mediated knockdown of RhoGDIβ in INS-1 832/13 cells significantly attenuated glucose-induced Rac1 activation without affecting its translocation and membrane association. Further, suppression of RhoGDIβ expression exerted minimal effects on GSIS at the height of inhibition of Rac1 activation, suggesting divergent effects of RhoGDIβ on Rac1 activation and insulin secretion in the glucose-stimulated β-cell. We provide the first evidence for the expression of RhoGDIβ in rodent and human β-cells, and its differential regulatory roles of this protein in G protein activation and GSIS. Abbreviations : Arf6: ADP ribosylation factor; Cdc42: Cell Division Cycle; GAP: GTPase-activating protein; GDI: GDP dissociation inhibitor; GDIα: GDP dissociation inhibitorα; GDIβ: GDP dissociation inhibitorβ; GEF: Guanine nucleotide exchange factor; GSIS: Glucose-stimulated insulin secretion; Rac1: Ras-Related C3 Botulinum Toxin Substrate 1