Abstract
Insulin resistance is a major contributor to macro- and microvascular complications,
particularly in the presence of the metabolic syndrome, and is also associated with
polycystic ovary syndrome. Impaired nitric oxide metabolism and endothelial function
are important components of the vascular disease. Increasing the bioavailability of
arginine, the precursor of nitric oxide, thus potentially offers protection against
end-stage disease. We have recently demonstrated that dietary supplementation with
a novel silicate inositol arginine complex reduces vasculopathy and glomerular sclerosis
in the insulin-resistant JCR:LA-cp rat. The objective of this study was to address the absorption of, and the underlying
metabolic alterations caused by, the arginine silicate inositol complex and arginine
HCl (as a reference agent) in obese insulin-resistant male and female JCR:LA-cp rats. Male and female rats were treated with the preparations at 1.0 mg/(kg d) (expressed
as arginine HCl) from 8 to 12 and 12 to 18 weeks of age, respectively. Obese female,
but not male, rats treated with the arginine silicate inositol complex showed a reduced
rate of weight gain without concomitant reduction in food intake. Plasma silicon levels
were raised very significantly in arginine silicate–treated rats, consistent with
significant absorption of the complex. In male rats, arginine levels were elevated
by treatment with arginine silicate only; and female rats responded to both preparations.
Plasma concentrations of oxides of nitrogen in rats treated with the silicate complex
showed a dimorphism, decreasing in male and increasing in female rats. Fasting insulin
levels were elevated in male rats treated with the arginine silicate complex, whereas
fasting and postprandial insulin levels were decreased in female rats. Furthermore,
female, but not male, rats treated with either of the arginine preparations showed
significant reductions in cholesterol, triglyceride, and phospholipid concentrations.
We conclude that the arginine silicate inositol complex is absorbed efficiently, raising
plasma arginine levels, and is more biologically effective than the free amino acid
hydrochloride. This has different beneficial metabolic effects in both sexes of an
animal model of insulin resistance and cardiovascular disease, consistent with reduction
in end-stage disease.
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Article info
Publication history
Accepted:
May 8,
2007
Received:
September 29,
2006
Identification
Copyright
© 2007 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
