The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 11 No. 7 • December 2008


L-Arginine Prevents Metabolic Effects of High Glucose in Diabetic Mice

High glucose levels and blood lipids are responsible for most of the negative effects of diabetes and increasing levels of glucose and lipids also contribute importantly to the aging process. A new paper1 reports that L-arginine supplementation (delivered via subcutaneous osmotic pumps) of 50 mg/kg/day in diabetic (insulin-deficient—type 1—diabetes induced by streptozotocin) mice “markedly prevented tissue sorbitol accumulation, ROS [reactive oxygen species] generation, and PKC [protein kinase C] activation—three critical biochemical abnormalities associated with hyperglycemic injury. Taken together, these results support the novel concept that NO [nitric oxide] production or availability during diabetes is a key step that is mechanistically linked to the major biochemical effects of high glucose.”1

The untreated diabetic mice had 2- to 2.4-fold higher levels of plasma triglyceride than the non-diabetic controls. L-arginine treatment reduced the plasma triglycerides of the diabetic mice to levels not significantly different than that of the controls. While the diabetic animals had significantly increased (1.3-fold compared to controls) circulating levels of soluble intercellular adhesion molecule, a marker of vascular inflammation, this was completely prevented by L-arginine.

L-arginine also completely abolished the accumulation of sorbitol (increased by 5.8-fold in the kidneys of the diabetic mice), by inhibiting aldose reductase, an enzyme that catalyzes the first and rate-limiting step of the polyol pathway that creates sorbitol from glucose.

The authors explain that activation of PKC, particularly the PKCbetaII isoform, “has been associated with several features of glucose toxicity, including microvascular changes, increased vascular ROS generation, and endothelial and macrophage activation. In particular, hyperglycemia-induced endothelial dysfunction [failure of blood vessels to dilate to response to physiological stimuli such as acetylcholine] in humans is prevented by pretreatment with the PKCbetaII-specific inhibitor ruboxistaurin. Hence, our observation that increasing NO by simple L-arginine supplementation prevents PKC activation supports the underlying hypothesis that AR [aldose reductase] plays a critical role in the early stages of diabetic complications and that inhibition of this enzyme by increasing NO prevents one of the major causes of diabetic complications, i.e., PKC activation.”1

Scaled as a percentage of the diet of these mice, this is roughly equivalent to 250 mg of supplemental arginine for a human. Scaled by body weight, this is 5 grams of supplemental arginine per day for a 100 kg human.

We get our supplemental L-arginine from InnerPower Plus™, our formulation of NO pathway constituents that includes arginine (6 grams per serving) and citrulline plus factors that affect pathways that crosstalk (interact) with the NO pathway, including choline.

Reference

  1. West et al. L-Arginine prevents metabolic effects of high glucose in diabetic mice. FEBS Lett 582:2609-14 (2008).

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