Je. Albina et B. Mastrofrancesco, MODULATION OF GLUCOSE-METABOLISM IN MACROPHAGES BY PRODUCTS OF NITRIC-OXIDE SYNTHASE, The American journal of physiology, 264(6), 1993, pp. 1594-1599
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.