Signal transduction via TRPM3 channels in pancreatic β-cells

Transient receptor potential melastatin 3 (TRPM3) channels are non-selective cation channels that are expressed in insulinoma cells and pancreatic beta-cells. Stimulation of TRPM3 with the neurosteroid pregnenolone sulfate induces an intracellular signaling cascade, involving a rise in intracellular Ca2+ concentration, activation of the protein kinases Raf and ERK, and a change in the gene expression pattern of the cells. In particular, biosynthesis of insulin is altered following activation of TRPM3 by pregnenolone sulfate. Moreover, a direct effect of TRPM3 stimulation on insulin secretion has been reported. The fact that stimulation of TRPM3 induces a signaling cascade that is very similar to the signaling cascade induced by glucose in beta-cells suggests that TRPM3 may influence main functions of pancreatic beta-cells. The view that TRPM3 represents an ionotropic steroid receptor of pancreatic beta-cells linking insulin release with steroid hormone signaling is discussed.