Biochemical and Biophysical Research Communications, Vol.284, No.4, 918-922, 2001
The imidazoline RX871024 stimulates insulin secretion in pancreatic beta-cells from mice deficient in K-ATP channel function
Effects of the imidazoline compound RX871024 on cytosolic free Ca2+ concentration ([Ca2+](i)) and insulin secretion in pancreatic beta -cells from SUR1 deficient mice have been studied. In beta -cells from wild-type mice RX871024 increased [Ca2+](i) by blocking ATP-dependent K+-current (K-ATP) and inducing membrane depolarization. In beta -cells lacking a component of the K-ATP-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 K-ATP-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 K-ATP-channel.