title: Effect of L-arginine-nitric oxide system on chemical-induced diabetes mellitus.
abstract: 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 NG-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.
authors.affiliation: Division of Internal Medicine, L.V. Prasad Eye Institute, Hyderabad, India.
authors.forename: I K
authors.initials: IK
authors.lastname: Mohan
authors.forename: U N
authors.initials: UN
authors.lastname: Das
mesh_terms: D000496:Alloxan; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D007328:Insulin; D007657:Ketone Bodies; D008054:Lipid Peroxides; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019344:Lactic Acid; D000496:Alloxan; D001120:Arginine; D019001:Nitric Oxide Synthase