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.

FEBS Letters
|July 1, 2008
PubMed

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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