DICHLOROACETATE INHIBITS GLYCOLYSIS AND AUGMENTS INSULIN-STIMULATED GLYCOGEN-SYNTHESIS IN RAT MUSCLE
DICHLOROACETATE INHIBITS GLYCOLYSIS AND AUGMENTS INSULIN-STIMULATED GLYCOGEN-SYNTHESIS IN RAT MUSCLE
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DOI：
10.1172/jci112851
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发表时间：
1987-02-01
影响因子：
15.9
通讯作者：
CURNOW, RT
中科院分区：
文献类型：
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作者：
CLARK, AS;MITCH, WE;CURNOW, RT
二氯醋酸盐（DCA）治疗期间血浆乳酸盐的减少归因于乳酸盐氧化的刺激。为了确定DCA是否也抑制乳酸产生，我们测量了与DCA和胰岛素孵育的进食和禁食大鼠肌肉中的葡萄糖代谢。DCA增加葡萄糖-6-磷酸，糖原合酶的变构修饰剂，50%，并增加肌糖原合成和糖原含量> 25%。乳酸释放下降;糖酵解抑制占减少的> 80%。这与细胞内AMP的减少有关，但柠檬酸盐或ATP没有变化。当通过提高细胞外乳酸来增加乳酸氧化时，糖酵解降低（r = -0.91），表明乳酸氧化调节糖酵解。当肌肉乳酸产生受到热损伤的极大刺激时，DCA增加糖原合成，使糖原含量正常化，并抑制糖酵解，从而减少乳酸释放。DCA对肌肉乳酸代谢的主要作用是抑制糖酵解。
The decrease in plasma lactate during dichloroacetate (DCA) treatment is attributed to stimulation of lactate oxidation. To determine whether DCA also inhibits lactate production, we measured glucose metabolism in muscles of fed and fasted rats incubated with DCA and insulin. DCA increased glucose-6-phosphate, an allosteric modifier of glycogen synthase, .apprx. 50% and increased muscle glycogen synthesis and glycogen content > 25%. Lactate release fell; inhibition of glycolysis accounted for > 80% of the decrease. This was associated with a decrease in intracellular AMP, but no change in citrate or ATP. When lactate oxidation was increased by raising extracellular lactate, glycolysis decreased (r = -0.91), suggesting that lactate oxidation regulates glycolysis. When muscle lactate production was greatly stimulated by thermal injury, DCA increased glycogen synthesis, normalized glycogen content, and inhibited glycolysis, thereby reducing lactate release. The major effect of DCA on lactate metabolism in muscle is to inhibit glycolysis.