胰岛素抵抗及高血糖对GFAT活性的影响

Study on GFAT activity stimulated by insulin resistance and hyperglycaemia

分别观察了胰岛素抵抗和高血糖水平对己糖胺途径限速酶GFAT活性的影响.在alloxan高血糖小鼠模型中,与正常对照组比较,血清果糖胺水平升高了15.9%,肾组织GFAT活性升高了32.8%;经胰岛素治疗后,血清果糖胺水平降低了9.7%,其肾组织GFAT活性也降低了l9.4%.在高糖高脂饲料诱导的胰岛素抵抗的IR小鼠中,与同批正常对照组比较,正糖钳实验中稳态时葡萄糖输注率G IR值降低了69.3%,胰岛素耐量实验中的AUC值升高了38.1%,其肾脏组织GFAT活性也增加了26.6%.在胰岛素诱导的具有胰岛素抵抗的IR-H IR c细胞模型中,与正常H IR c细胞比较,其10、25 nmol/L胰岛素诱导的葡萄糖摄取能力分别降低了25.3%、21.1%,而GFAT活性分别增加了29.7%、46.5%.可见,GFAT活性与一段时间的平均血糖水平和胰岛素抵抗状态密切正相关.

The GFAT activity stimulated by the hyperglycaemia （HG） and insulin resistance （IR） is observed in this paper. The GFAT activity was measured by GDH enzyme method. The insulin sensitivity was evaluated by the insulin tolerant test （ITT） and the value of the glucose infusion rate （GIR） in the hyperinsulinemic-euglycemic clamp test in vivo, and by the insulin-induced glucose uptake in vitro. In the diabetic mice stimulated by alloxan, comparing with the normal control, the serum fructosamine is increased by 15.9%, its renal GFAT activity was enhanced by 32.8% ; after the administration with insulin for 4 weeks, the increased levels of serum fructosamine and the renal GFAT activity were reversed by 9. 7% and 19.4%, respectively. In the insulin resistant IR mice induced by high-caloric diet in C57BL/6N mice, comparing with the age-matched mice control, the level of GIR is decreased by 69.3%, AUC in ITT increased by 38.1%, and the renal GFAT activity elevated by 26.6%. In insulin resistant IR-HIRc cells induced by the long-action insulin administration for 36 h, the ability of glucose uptake induced by 10 and 25 nmol/L insulin was decreased by 25. 3% and 21. 1%, and the GFAT activity was increased by 29.7% and 49.7%, respectively, comparing with those in HIRc cells. In conclusion, the GFAT activity was correlated with the average level of blood glucose and insulin resistance.