Dichloroacetate-lnduced Changes in Liver of Normal and Diabetic Rats
Dichloroacetate-lnduced Changes in Liver of Normal and Diabetic Rats
复制标题
二氯乙酸引起正常和糖尿病大鼠肝脏的变化
DOI：
10.3181/00379727-149-38905
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发表时间：
1975
影响因子：
--
通讯作者：
T. Yoneyama
中科院分区：
文献类型：
--
作者：
James W. Anderson;D. Karounos;T. Yoneyama
总结以1000 mg/天/kg大鼠体重的剂量对正常（非糖尿病）和链脲佐菌素糖尿病大鼠经口给予二氯乙酸盐（DCA）。一组糖尿病动物经口和腹腔内接受DCA。DCA治疗降低了糖尿病动物的血糖值，但没有改变非糖尿病大鼠的值。与未治疗动物相比，DCA治疗的非糖尿病动物和DCA治疗的糖尿病动物中葡萄糖激酶和丙酮酸激酶的肝脏活性均显著降低。然而，DCA治疗伴随着显着增加葡萄糖-6-磷酸脱氢酶和苹果酸酶的活动在非糖尿病和糖尿病动物。葡萄糖-6-磷酸脱氢酶在DCA治疗的非糖尿病动物中高3倍，而苹果酸酶活性在治疗的动物中比在未治疗的动物中观察到的高10倍。在DCA治疗的糖尿病动物中观察到这些酶的类似变化，尽管幅度较小。虽然DCA治疗伴随着非糖尿病和糖尿病动物肝脏湿重的显著增加，但通过光学或电子显微镜观察未观察到形态学变化。我们的观察加上那些以前的研究人员表明，DCA治疗可能有一个重要的作用，丙酮酸代谢，并可能降低血糖浓度，通过抑制肝纤维化。
Summary Dichloroacetate (DCA) was administered orally to normal (nondiabetic) and streptozotocin-diabetic rats in a dose of 1000 mg/day/kg rat wt. One group of diabetic animals Received DCA both orally and intraperitoneally. DCA therapy lowered the blood glucose values of diabetic animals but did not alter values in nondiabetic rats. The hepatic activity of glucokinase and pyruvate kinase were significantly lower in both DCA-treated nondiabetic and DCA-treated diabetic animals than values observed for untreated animals. However, DCA therapy was accompanied by remarkable increases in the activities of glucose-6-phosphate dehydrogenase and malic enzyme in both nondiabetic and diabetic animals. Glucose-6-phosphate dehydrogenase was 3-fold higher in DCA-treated nondiabetic animals whereas malic enzyme activity was 10-fold higher in the treated animals than observed in the untreated animals. Similar changes, although smaller in magnitude, were observed for these enzymes in the DCA-treated diabetic animals. Although DCA therapy was accompanied by a significant increase in the wet weights of the liver for both nondiabetic and diabetic animals, no morphological changes were seen by light or electron microscopy. Our observations coupled with those of previous investigators suggest that DCA therapy may have an important role in pyruvate metabolism and may lower the blood glucose concentration by inhibiting hepatic gluconeogenesis.