Key result
L-arginine prevents metabolic abnormalities and a ~10-fold increase in MMP-9 in sucrose-fed rats.
Why the study?
Sucrose-induced insulin resistance may increase cardiac matrix metalloproteinases expression and matrix remodelling, and the effect of L-arginine supplementation on these changes is unclear.
Does L-arginine supplementation prevent sucrose-induced metabolic abnormalities and elevated cardiac expression of matrix metalloproteinases in insulin-resistant rats?
Does L-arginine supplementation prevent sucrose-induced metabolic abnormalities and elevated cardiac expression of matrix metalloproteinases in insulin-resistant rats?
L-arginine supplementation prevents sucrose-induced insulin resistance, hyperlipidaemia, and cardiac matrix remodelling in a rat model.
No immediate clinical role; leaves open translation of L-arginine effects on MMP-9 to human insulin resistance.
BACKGROUND: The study was performed to determine whether sucrose-induced insulin resistance could increase the expression of cardiac matrix metalloproteinases (MMPs), indices of matrix remodelling, and whether the addition of 1.25 g day(-1) of L-arginine (ARG) to a sucrose diet could prevent both the sucrose-induced metabolic abnormalities and elevated cardiac expression of matrix metalloproteinases in an insulin resistant stage that precedes frank type 2 diabetes. MATERIALS AND METHODS: Experiments were performed on 38 male Sprague-Dawley rats, 16 rats maintained a standard chow diet (ST), 12 rats were switched to a sucrose enriched diet (SU) and 10 rats to a sucrose plus L-arginine (1.25 g day(-1)) enriched diet (SU + ARG) for a period of 8 weeks. After 8 weeks of different diets, an intravenous glucose tolerance test (IVGTT) was performed and samples were drawn for the measurements of insulin, glucose, triglycerides, free fatty acids (FFA), plasma cyclic guanosine-monophosphate (c-GMP) and retroperitoneal, omental, epididymal fat pad and heart were dissected and weighed. RESULTS: At the end of the study, retroperitoneal fat, heart weight/body weight ratio, fasting plasma glucose, serum insulin, and serum triglyceride levels and integrated insulin area after IVGTT were significantly higher in SU than in SU + ARG and ST. All these parameters were comparable between SU + ARG and ST animals. FFA levels were significantly different among groups, with highest levels in SU and lowest levels in ST. Fasting plasma c-GMP levels and the integrated c-GMP area after IVGTT, an index of nitric oxide activity, were significantly lower in SU than in SU + ARG and ST, the result was similar in SU + ARG and in ST MMP-9 protein expression increased 10.5-fold, MMP-2 protein expression increased 2.4-fold and the expression of tissue inhibitors of metalloproteinase (TIMP-1) increased 1.7-fold in SU rats as compared to ST animals. This was accompanied with a significant increase of cardiac triglyceride concentrations. In contrast, cardiac MMP-9, MMP-2, and TIMP-1 protein expressions were not different between SU + ARG and ST animals. Cardiac triglyceride levels were not significantly different between SU + ARG and ST rats. CONCLUSIONS: SU rats developed insulin resistance and hyperlipidaemia, accompanied with increased fat deposition in the heart and enhanced MMP protein expression. Conversely, ARG supplementation prevents these metabolic abnormalities and restored MMP/TIMP-1 balance.
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Monti et al. (2008) studied Sucrose-induced insulin resistance and cardiac matrix remodelling (n=38). L-arginine vs. Sucrose enriched diet (SU) and standard chow diet (ST) was evaluated on Cardiac matrix metalloproteinases (MMP-9, MMP-2) and TIMP-1 protein expression. L-arginine supplementation in sucrose-fed rats prevented metabolic abnormalities and restored the MMP/TIMP-1 balance, preventing the 10.5-fold increase in MMP-9 seen with sucrose alone.
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