EFFECT OF L-ARGININE-NITRIC OXIDE SYSTEM ON CHEMICAL-INDUCED DIABETES-MELLITUS

Several in vitro studies have suggested that nitric oxide may be the m ediator of cytokine-induced beta-cell destruction. On the other hand, in vivo studies have given conflicting results: some studies suggestin g that nitric oxide synthase inhibitors do not suppress streptozotocin -induced diabetes in mice, while others revealed that nitric oxide syn thase inhibitors can reduce the incidence of insulin-dependent diabete s mellitus in rats. The results of the present study indicate that all oxan-induced diabetes in the male Wistar rats can be abrogated to a la rge extent by prior and simultaneous administration of the precursor o f nitric oxide, L-arginine, where as N-G-monomethy-L-arginine (L-NMMA) , a specific inhibitor of nitric oxide synthase, can completely block the beneficial action of L-arginine. Sodium nitroprusside, a nitric ox ide donor, also showed significant inhibitory effect on the severity o f diabetes induced by alloxan. Alloxan treatment reduced nitric oxide generation, whereas L-arginine and sodium nitroprusside, when given al ong with alloxan, enhanced nitric oxide production to control values. Induction of diabetes by alloxan in the experimental animals was assoc iated with a marked elevation in plasma lactate, ketone body, and lipi d peroxide levels with a simultaneous fall in plasma insulin and nitri c oxide levels. Alloxan-induced diabetes also induced a fall in the le vels of anti-oxidant enzymes such as superoxide dismutase, glutathione reductase, and total glutathione, and antioxidants: vitamin E and cer uloplasmin, and an increase in glutathione peroxidase and glutathione- S-transferase. All these biochemical abnormalities and antioxidant lev els have improved to near normal levels in animals treated with insuli n, L-arginine, and sodium nitroprusside. From the results of the prese nt study, it is apparent that L-arginine and nitric oxide can prevent alloxan-induced beta-cell damage, and the development of diabetes, and restore the antioxidant status to near normal levels. (C) 1998 Elsevi er Science Inc.