title: Stimulation of insulin secretion in clonal BRIN-BD11 cells by the imidazoline derivatives KU14r and RX801080.
abstract: The imidazoline derivatives KU14R and RX801080 have each been reported to antagonize imidazoline-stimulated insulin secretion. This study investigated the effects of a range of concentrations of both KU14R and RX801080 on insulin secretion from the clonal pancreatic beta cell line, BRIN-BD11. In the presence of a stimulatory (8.4 m m) glucose concentration, both KU14R (50-200 microm;P< 0.01 to P< 0.001) and RX801080 (50-200 microm;P< 0.01 to P< 0.001) were found to dose-dependently stimulate insulin secretion. The imidazoline efaroxan (200 microm) stimulated insulin secretion (P< 0.001) from BRIN-BD11 cells. This insulinotropic effect was significantly augmented by KU14R (100-200 microm;P< 0.01 to P< 0.001) and RX801080 (200 microm;P< 0.05). Insulin secretion from BRIN-BD11 cells was also stimulated by the novel guanidine derivative BTS 67 582 (200 microm;P< 0.001). This secretagogue action was augmented both by KU14R (25-200 microm;P< 0.001) and by RX801080 (25-200 microm;P< 0.05 to P< 0.001). It is concluded that, rather than acting as antagonists of imidazoline-induced insulin secretion, the imidazoline derivatives KU14R and RX801080 are themselves potent insulinotropic agents.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, BT52 1SA, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ball
authors.forename: P R
authors.initials: PR
authors.lastname: Flatt
authors.forename: N H
authors.initials: NH
authors.lastname: McClenaghan
mesh_terms: D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects
chemical_list: D001572:Benzofurans; D007093:Imidazoles; D007328:Insulin; C106086:KU 14R; C042254:S 9871