MODULATION OF GLUCOSE-METABOLISM IN MACROPHAGES BY PRODUCTS OF NITRIC-OXIDE SYNTHASE

Nitric oxide (NO) is a product of L-arginine metabolism that suppresse s cellular oxidative metabolism through the inhibition of tricarboxyli c acid cycle and electron transport chain enzymes. The impact of NO sy nthase (NOS) activity on specific pathways of glucose metabolism in fr eshly harvested and overnight-cultured rat resident peritoneal macroph ages, at rest and after stimulation with zymosan, was investigated usi ng radiolabeled glucose. NOS activity was modulated through the L-argi nine concentration in culture media and the use of its specific inhibi tor, N(G)-monomethyl-L-arginine, and quantitated using radiolabeled L- arginine. Results demonstrated that NOS activity was associated with i ncreased glucose disappearance, glycolysis, and hexose monophosphate s hunt activity and, in line with the known inhibition of oxidative meta bolism associated with the production of NO, with a decrease in the fl ux of glucose and butyrate carbon through the tricarboxylic acid cycle . In addition, the relative increase in glucose utilization that follo ws zymosan stimulation was enhanced by treatments that suppressed NOS activity. These results demonstrate that the characteristics of glucos e metabolism by macrophages are, to a significant extent, determined b y products of NOS.