Blackshear P J, Holloway P A, Aberti K G
Biochem J. 1975 Jun;148(3):353-62. doi: 10.1042/bj1480353b.
Experiments were performed in which the effects of inhibiting gluconeogenesis on ketone-body formation were examined in vivo in starved and severely streptozotocin-diabetic rats. The infusion of 3-mercaptopicolinate, an inhibitor of gluconeogenesis (DiTullio et al., 1974), caused decreases in blood [glucose] and increases in blood [lactate] and [pyruvate] in both normal and ketoacidotic rats. Patterns of liver gluconeogenic intermediates after 3-mercaptopicolinate infusion suggested inhibition at the level of phosphoenolpyruvate carboxykinase. This was confirmed by measurement of hepatic oxaloacetate concentrations which were increased 5-fold after 3-mercaptopicolinate administration. The infusion of 3-mercaptopicolinate caused a decrease in total ketone-body concentrations of 30% in starved rats and 73% in the diabetic animals. Blood glycerol and hepatic triglyceride concentrations remained unchanged. The decreases in ketone-body concentrations were associated with increases in the calculated hepatic cytosolic and mitochondrial [NADH]/[NAD+] ratios. The decrease in ketogenesis seen after inhibition of gluconeogenesis may have resulted from an inhibition of hepatic fatty acid oxidation by the more reduced mitochondrial redox state. It was concluded that gluconeogenesis may stimulate ketogenesis by as much as 30% in severe diabetic ketoacidosis.
进行了相关实验，研究在饥饿和严重链脲佐菌素诱导的糖尿病大鼠体内，抑制糖异生对酮体生成的影响。输注3-巯基吡啶甲酸盐（一种糖异生抑制剂，迪图利奥等人，1974年），导致正常大鼠和酮症酸中毒大鼠的血糖浓度降低，血乳酸和丙酮酸浓度升高。输注3-巯基吡啶甲酸盐后肝脏糖异生中间产物的模式表明在磷酸烯醇式丙酮酸羧激酶水平受到抑制。这通过测量肝草酰乙酸浓度得到证实，输注3-巯基吡啶甲酸盐后其浓度增加了5倍。输注3-巯基吡啶甲酸盐使饥饿大鼠的总酮体浓度降低了30%，糖尿病动物降低了73%。血甘油和肝甘油三酯浓度保持不变。酮体浓度的降低与计算得出的肝脏胞质和线粒体[NADH]/[NAD+]比值升高有关。抑制糖异生后酮生成减少可能是由于线粒体氧化还原状态更加还原，抑制了肝脏脂肪酸氧化。得出的结论是，在严重糖尿病酮症酸中毒中，糖异生可能刺激酮生成多达30%。
