| ObjectiveInsulin resistance plays a major role in the development of type 2 diabetes mellitus. A previous study showed an inverse relationship between fasting plasma fatty acid concentrations and insulin sensitivity. Free fatty acid impairs insulin activity with many mechanisms. Oxidative stress is an important part in these mechanisms. Several clinical trials have demonstrated improved insulin sensitivity with the antioxidants vitamin C, vitamin E, α - lipoic acid and glutathione. But the effect of the antioxidant N - acetylcysteine on insulin resistance remains unclear. The objective of this study was to prove free fatty acid - induced insulin resistance with euglycemic - hyperinsulinemic clamp which is the internationally accepted as "golden standard "to determine insulin resistance and assess the effect of N - acetylcysteine on this resistance.Methods1. Animal models: 24 normal female Wistar rats were anesthetized with 10% chloral hydrate(0. 35ml/kg) , Indwelling catheters were inserted into the right internal jugular vein for infusions and the left carotid artery for sampling. Both catheters were filled with a mixture of 60% polyvinylpyrrolidone and hepa-rin(1 ,000U/ml) to maintain patency and were closed at the end with a metal pin.2. Euglycemic - hyperinsulinemic clamp: After 3 days period of postsur-gery recovery, the rats fasted overnight were randomly divided into 4 equal groups, one of which received IH infusion(20% intralipid + 20U/ml heparin,5.5ul/min) , one of which received NAC infusion(N - acetylcysteine,0. 35mg· kg-1 · min-1 ) ,one of which received IH + NAC infusion,another group was a saline(5ul/min) -treated control. Insulin sensitivity was assessed using a 2- h euglycemic - hyperinsulinemic clamp after the 5 - h infusion period during which the infusion mentioned above was continued. An infusion of insulin ( 5 mU· kg-1 · min-1 ) and 25% glucose was given intravenously through the jugular catheter during the clamp. To maintain euglycemia, the glucose infusion rate (GIR) was adjusted according to frequent glycemic determination (every 5 min to 10 min). All studies were performed in awake rats. Blood samples for insulin and FFA were taken at 0min, 280min, 290min, 300min, 340min, 380min, 400min,410min,420min.3. Statistical analysis: Statistical calculations were performed using SPSS software 11.5. All data were expressed as means ±SD. Differences between the groups or in each group were tested by one - way analysis of variance. Significance was accepted at P <0.05.Results1. There were no significant differences in the insulin levels between different groups. But the insulin levels in the IH group were higher than the other groups.2. IH elevated plasma FFA levels from 515.54 ±391.20umol/L to 1623.72 ±698.21umol/L, and there were significant differences between the IH group and the control group at 280min,290min,300min,340min,380 min,400min, 410 min,420min,P <0.05. The FFA levels of the IH + NAC group were signifi-canty lower than the IH group, P < 0. 05. It showed the infusion of NAC decreased the elevation of FFA caused by IH infusion.3. The euglycemic - hyperinsulinemic clamp showed the GIR in the IH group was significantly lower than the control group (14.25 ±9.00mg ·kg-1 · min-1 vs 28. 01 ±7. 78mg · kg-1 · min-1, P <0. 05). The GIR of the IH + NAC group (18.46 ±9.76mg kg-1 · min-1)was higher than the IH group,but it was no significant difference compared with the IH group or the control group. |
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