Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aldehyde Reductase / antagonists & inhibitors
-
Animals
-
Aortitis / etiology
-
Aortitis / metabolism
-
Aortitis / prevention & control*
-
Arginine / therapeutic use*
-
Diabetes Mellitus, Experimental / complications
-
Diabetes Mellitus, Experimental / metabolism
-
Diabetes Mellitus, Type 1 / complications*
-
Diabetes Mellitus, Type 1 / metabolism
-
Disease Models, Animal
-
Glutathione / metabolism
-
Heart Diseases / etiology
-
Heart Diseases / metabolism
-
Heart Diseases / prevention & control*
-
Hyperglycemia / complications*
-
Hyperglycemia / metabolism
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Nitric Oxide / biosynthesis*
-
Phosphorylation
-
Polymers / metabolism
-
Protein Kinase C / metabolism
-
Protein Kinase C beta
-
Sorbitol / metabolism
-
Superoxides / metabolism
Substances
-
Polymers
-
polyol
-
Superoxides
-
Nitric Oxide
-
Sorbitol
-
Arginine
-
Aldehyde Reductase
-
Protein Kinase C
-
Protein Kinase C beta
-
Glutathione