Decreased production of nitric oxide by LPS-treated J774 macrophages in high-glucose medium.

We investigated the effect of high glucose levels on nitric oxide (NO) production by J774 macrophages treated with LPS. High concentrations of glucose inhibited the accumulation of nitrite, an indicator of NO production, and the steady state levels of inducible NO synthase mRNA were significantly reduced. While phorbol myrystate acetate mimicked the inhibition of NO production by glucose, the aldose reductase inhibitor ONO2235 did not alter NO production under normal or high glucose conditions. High glucose levels also prevented the increase in cellular levels of tetrahydrobiopterin, an essential cofactor of NO synthase. The reduction of inducible NO production by elevated glucose levels may therefore be involved in the pathophysiology of diabetes.