Abstract
Effects of the imidazoline compound RX871024 on cytosolic free Ca2+ concentration ([Ca2+]i) and insulin secretion in pancreatic β-cells from SUR1 deficient mice have been studied. In β-cells from wild-type mice RX871024 increased [Ca2+]i by blocking ATP-dependent K+-current (KATP) and inducing membrane depolarization. In β-cells lacking a component of the KATP-channel, SUR1 subunit, RX871024 failed to increase [Ca2+]i. However, insulin secretion in these cells was strongly stimulated by the imidazoline. Thus, a major component of the insulinotropic activity of RX871024 is stimulation of insulin exocytosis independently from changes in KATP-current and [Ca2+]i. This means that effects of RX871024 on insulin exocytosis are partly mediated by interaction with proteins distinct from those composing the KATP-channel.
