Effect of l-arginine–nitric oxide system on chemical-induced diabetes mellitus

• Published in: Free radical biology & medicine 1998-11, Vol.25 (7), p.757-765
• Main Authors: Mohan, I.Krishna, Das, U.N.
• Format: Article
• Language: English
• Subjects: Alloxan; Animals; Antioxidants; Antioxidants - metabolism; Arginine - pharmacology; Arginine - therapeutic use; Diabetes Mellitus, Experimental - prevention & control; Enzyme Inhibitors - pharmacology; Free radical; Insulin; Insulin - blood; Insulin-dependent diabetes mellitus; Ketone Bodies - blood; l-Arginine; Lactic Acid - blood; Lipid Peroxides - blood; Male; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitroprusside - pharmacology; omega-N-Methylarginine - pharmacology; Rats; Rats, Wistar
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(98)00129-4

Several in vitro studies have suggested that nitric oxide may be the mediator of cytokine-induced beta-cell destruction. On the other hand, in vivo studies have given conflicting results: some studies suggesting that nitric oxide synthase inhibitors do not suppress streptozotocin-induced diabetes in mice, while others revealed that nitric oxide synthase inhibitors can reduce the incidence of insulin-dependent diabetes mellitus in rats. The results of the present study indicate that alloxan-induced diabetes in the male Wistar rats can be abrogated to a large extent by prior and simultaneous administration of the precursor of 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 oxide donor, also showed significant inhibitory effect on the severity of diabetes induced by alloxan. Alloxan treatment reduced nitric oxide generation, whereas l-arginine and sodium nitroprusside, when given along with alloxan, enhanced nitric oxide production to control values. Induction of diabetes by alloxan in the experimental animals was associated with a marked elevation in plasma lactate, ketone body, and lipid peroxide levels with a simultaneous fall in plasma insulin and nitric oxide levels. Alloxan-induced diabetes also induced a fall in the levels of anti-oxidant enzymes such as superoxide dismutase, glutathione reductase, and total glutathione, and antioxidants: vitamin E and ceruloplasmin, and an increase in glutathione peroxidase and glutathione- S-transferase. All these biochemical abnormalities and antioxidant levels have improved to near normal levels in animals treated with insulin, l-arginine, and sodium nitroprusside. From the results of the present 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.