The role of nitric oxide in the development of streptozotocin-induced diabetes mellitus: Experimental and clinical implications

The overproduction of the free radical nitric oxide (NO) by activated immun ocompetent cells with subsequent development of local oxidative stress is s upposed to be one of the possible pathophysiological mechanisms of beta-cel l damage during streptozotocin-induced diabetes. The blockade of increased NO production by simultaneous administration of NO-synthase inhibitors part ially suppresses the hyperglycemia and the increase of glycated hemoglobin concentration. Here we summarize the current state of knowledge concerning the modulation of streptozotocin-induced diabetes development by treatment with NO-synthase inhibitors including the partial inhibition of the changes in serum leptin levels. The differences in the reaction to streptozotocin administration between wild type mice and inducible NO-synthase knockout mi ce are also discussed. The overproduction of NO during the development of s treptozotocin-induced diabetes is probably an important part of the complex autoimmune reaction which leads to the destruction of pancreatic beta-cell s. Further clarification of the role of nitric oxide in streptozotocin-indu ced diabetes development could have important clinical implications.