L-Arginine prevents metabolic effects of high glucose in diabetic mice.
We tested the hypothesis that activation of the polyol pathway and protein kinase C (PKC) during diabetes is due to loss of NO. Our results show that after 4 weeks of streptozotocin-induced diabetes, treatment with L-arginine restored NO levels and prevented tissue accumulation of sorbitol in mice, which was accompanied by an increase in glutathiolation of aldose reductase. L-Arginine treatment decreased superoxide generation in the aorta, total PKC activity and PKC-beta(II) phosphorylation in the heart, and the plasma levels of triglycerides and soluble ICAM. These data suggest that increasing NO bioavailability by L-arginine corrects the major biochemical abnormalities of diabetes.
West
Matthew B
MB
Institute of Molecular Cardiology and Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202, United States.
Ramana
Kota V
KV
Kaiserova
Karin
K
Srivastava
Satish K
SK
Bhatnagar
Aruni
A
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001025:Aortitis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001120:Arginine / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D013012:Sorbitol / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D011108:Polymers; C024617:polyol; D013481:Superoxides; D009569:Nitric Oxide; D013012:Sorbitol; D001120:Arginine; D000449:Aldehyde Reductase; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D005978:Glutathione