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L-Arginine prevents metabolic effects of high glucose in diabetic mice
Matthew B West1, Kota V Ramana, Karin Kaiserova
1Institute of Molecular Cardiology and Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40202, United States.
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.
Insights
L-arginine treatment in diabetic mice restored nitric oxide (NO) levels, preventing harmful biochemical changes. This suggests increasing NO bioavailability can correct major diabetes abnormalities.
Area of Science:
- Biochemistry
- Physiology
- Endocrinology
Background:
- Diabetes mellitus is associated with the activation of the polyol pathway and protein kinase C (PKC).
- The loss of nitric oxide (NO) bioavailability is hypothesized to be a key factor in these diabetic complications.
Purpose of the Study:
- To investigate the role of NO in the activation of the polyol pathway and PKC in diabetes.
- To determine if L-arginine supplementation can ameliorate diabetic biochemical abnormalities by restoring NO levels.
Main Methods:
- Streptozotocin-induced diabetes model in mice.
- Administration of L-arginine to diabetic mice.
- Measurement of NO levels, sorbitol accumulation, aldose reductase glutathiolation, superoxide generation, PKC activity and phosphorylation, plasma triglycerides, and soluble intercellular adhesion molecule-1 (ICAM).
Main Results:
- L-arginine treatment restored NO levels and prevented sorbitol accumulation in diabetic mice.
- Treatment increased aldose reductase glutathiolation, reduced aortic superoxide generation, and decreased total PKC activity and PKC-beta(II) phosphorylation in the heart.
- Plasma triglycerides and soluble ICAM levels were reduced by L-arginine treatment.
Conclusions:
- Loss of NO bioavailability contributes to polyol pathway and PKC activation in diabetes.
- L-arginine supplementation effectively restores NO levels and corrects major biochemical abnormalities associated with diabetes.
- Increasing NO bioavailability represents a potential therapeutic strategy for managing diabetic complications.
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