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 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 (200μm ;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 (25–200μm ;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.