Dual Role of Nitric Oxide in Pancreatic β-Cells

An involvement of inducible nitric oxide (NO) synthase (NOS) in pancreatic beta-cell degeneration during the process of type 1 diabetes has been well discussed. Recently, there is growing evidence for pivotal roles of constitutive NOS (cNOS) in beta-cells; the presence of NOS1 and NOS3 in pancreatic beta-cells and the effects of low-concentration NO, which is assumed to be derived from cNOS, on beta-cell functions have been reported. However, the roles of cNOS-derived NO in beta-cells are still under debate. One of the reasons seems to be that NO has multiple biological activities, which are dependent on its concentration. In beta-cells, NO has been shown to exert positive and negative regulation of insulin secretion and anti- and pro-apoptotic activities, which is likely to be dependent on concentrations. In this review article, we will describe the current understanding of the roles of NO in pancreatic beta-cells, especially focusing on cNOS-derived NO and its differential roles depending on concentrations.