Abstract
Nitric oxide (NO) is a signaling molecule which can play a role in pancreatic pathophysiology and is involved in regulation of beta cell mass. Nitric oxide is produced by the enzyme NO synthase (NOS). Nitric oxide synthase has three major isoforms; one of them, inducible NOS (iNOS) is expressed in almost every cell type. In healthy pancreatic tissues, iNOS immunoreactivity was demonstrated in islet of Langerhans cells, centroacinar cells and ductal cells. In addition, induction of islet iNOS was also demonstrated in acute pancreatitis, and type 1 and type 2 diabetes mellitus. When pancreatic beta cells come up against inflammatory cytokines, lipid stress or hyperglycemia, iNOS activation increases and the resulting high concentrations of NO produced causes cell dysfunction or death and therefore the insulin secretion is inhibited. However, the precise mechanism of iNOS expression and the occurrence of resulting beta-cell damage have not been truly clarified yet. Diabetogenesis cannot be completely prevented with iNOS inhibitors. Physiological and pathological limits of iNOS expression should be established and the mechanism of the damage on beta cells by over-expression should be defined and prevented.