Insulin resistance and hyperinsulinemia have recently been identified as independent determinants of several risk factors for cardiovascular disease. The generation of reactive oxygen species (ROS) may play an important role as a final common mediator by which glucose and insulin resistance might contribute to development of cardiovascular disease and hypertension. The aim of the present study was to evaluate changes on mRNA expression of antioxidant enzymes [catalase, Cu-Zn superoxide dismutase (Cu-ZnSOD), MnSOD], blood pressure and metabolic parameters in insulin resistance that follow feeding normotensive Wistar rats a high-fructose-enriched diet. In our investigation 26 normal male Wistar rats were fed a highfructose diet for 2 weeks (no.=14) or normal chow to serve as a control group (no.=12). In vivo insulin resistance was verified in a subgroup of control and fructose-fed rats by the euglycemic hyperinsulinemic clamp technique at 2 different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol/kg/min respectively. The glucose infusion rate (GIR) was not significantly different in the two groups during the submaximal infusion of insulin (1.4±0.8 mmol/kg/min in fructosefed rats vs 1.6±0.7 mmol/kg/min in control rats, NS) while in fructose-fed rats it was significantly lower (-29.8%) than in control rats during maximal infusion of insulin (2.6±0.3 mmol/kg/min vs 3.7±0.3 mmol/kg/min, p<0.05). Fructose feeding markedly reduced the expression of catalase mRNA and Cu-ZnSOD mRNA in the liver, catalase mRNA in the heart (p<0.05). A tendency of fructose feeding to reduce the expression of antioxidant enzymes in skeletal muscle and adipose tissue was also observed (NS). Fructose feeding also increased plasma uric acid (119.9±30.4 vs 42.1±10 μmol/l, p<0.05) and systemic blood pressure (128±4 vs 109±5 mmHg, p<0.05) respect to control animals. No significant changes were observed in plasma levels of glycemia and tryglycerides. Our study suggests that in non-hyperglycemic, fructose-fed insulin-resistant rats the expression of catalase is inhibited in liver and heart. This condition might lead to higher susceptibility to oxidative stress in insulin resistance. However, an adaptive cellular response to maintain the effectiveness of intracellular signaling pathways mediated by insulinactivated hydrogen peroxide generating systems may also be hypothesized.
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Cavarape, A., Feletto, F., Mercuri, F. et al. High-fructose diet decreases catalase mRNA levels in rat tissues. J Endocrinol Invest 24, 838–845 (2001). https://doi.org/10.1007/BF03343940
- High-fructose diet
- insulin resistance
- antioxidant enzymes
- oxidative stress