title: Rhes expression in pancreatic beta-cells is regulated by efaroxan in a calcium-dependent process.
abstract: The monomeric G-protein Rhes has been described to be present in pancreatic beta-cells, and a putative role in the control of insulin release has been proposed. Here, we show that treatment of beta-cells with the imidazoline insulin secretagogue efaroxan resulted in a concentration- and time-dependent increase in the expression of Rhes, which peaked after 4h of efaroxan exposure; thereafter, Rhes mRNA levels decreased. Marked stereoselectivity was displayed, with (-)-efaroxan (the selectively insulinotropic enantiomer) being much more effective than (+)-efaroxan at raising Rhes transcript levels. The mechanism by which Rhes gene expression is activated in beta-cells appears to require the influx of extracellular calcium and de novo protein synthesis, and is not directly associated with the release of insulin. The present results confirm our earlier proposal that Rhes is an imidazoline-regulated transcript in pancreatic beta-cells. Studies to understand the role of Rhes as a regulator of beta-cell function are, thus, warranted.
authors.affiliation: Institute of Cell Signalling, School of Biomedical Sciences, University of Nottingham, The Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Taylor
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Jackson
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
authors.forename: Sue L F
authors.initials: SL
authors.lastname: Chan
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D005905:Glyburide / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D048288:Imidazolines / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D007004:Hypoglycemic Agents; D007093:Imidazoles; D048288:Imidazolines; D012333:RNA, Messenger; C038806:1,4-dihydropyridine; D019204:GTP-Binding Proteins; C486702:RASD2 protein, human; C062597:efaroxan; D005905:Glyburide; D002118:Calcium