Stimulation of insulin secretion in clonal BRIN-BD11 cells by the imidazoline derivatives KU14R and RX801080

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 mM) glucose concentration, both KU14R (50-200 μM; P < 0.01 to P < 0.001) and RX801080 (50-200 μM; P < 0.01 to P < 0.001) were found to dose-dependently stimulate insulin secretion. The imidazoline efaroxan (200 μM) stimulated insulin secretion (P < 0.001) from BRIN-BD11 cells. This insulinotropic effect was significantly augmented by KU14R (100-200 μM; P < 0.01 to P < 0.001) and RX801080 (200 μM; P < 0.05). Insulin secretion from BRIN-BD11 cells was also stimulated by the novel guanidine derivative BTS 67 582 (200 μM; P < 0.001). This secretagogue action was augmented both by KU14R (25-200 μM; P < 0.001) and by RX801080 (25-200 μM; 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. (C) 2000 Academic Press.