Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus

Several studies have shown that the activities of delta-6-desaturase and de lta-5-desaturase are depressed in experimental diabetes and in humans with insulin- and non-insulin-dependent diabetes mellitus (type I and type II di abetes mellitus respectively). Furthermore, treatment with insulin is known to correct the defects in desaturases in rats and humans with diabetes, es pecially in type I. In a recent study, we demonstrated that L-arginine and nitric oxide can prevent alloxan-induced beta cell damage, and the severity of diabetes, and restore the antioxidant status to near normal levels. But , no information is available as to the relationship between L-arginine-nit ric oxide system and the metabolism of essential fatty acids in diabetes me llitus. In the present study, it was noted that the plasma levels of satura ted fatty acids: stearic and palmitic were increased where as unsaturated f atty acids such as oleic, linoleic, gamma-linolenic and eicosapentaenoic ac ids (OA, LA, GLA and EPA respectively) were decreased in alloxan-induced di abetic rats. In the liver phospholipid (PL) fraction, GLA, DGLA (dihomo-GLA ) and alpha-linolenic acid (ALA) were decreased in the alloxan-treated grou p; in the muscle PL fraction, LA, GLA and DGLA were low, whereas an increas e in the saturated fatty acid content was noted. L-arginine (the precursor of nitric oxide) and sodium nitroprusside (a nitric oxide donor) treatment of alloxan-induced diabetic rats enhanced the levels of LA, GLA and DGLA. F urther, nitric oxide synthase inhibitor, L-NMMA, prevented this beneficial action of L-arginine-nitric oxide system on essential fatty acid metabolism . The abnormalities in the essential fatty acid metabolism observed also re verted to normalcy following control of diabetes with insulin. These result s indicate that nitric oxide can enhance the activities of deita-6- and del ta-5 desaturases, which are depressed in diabetes, and suggests that there is a close interaction between L-arginine-nitric oxide system and the metab olism of essential fatty acids. (C) 2000 Harcourt Publishers Ltd.