Bartels P D, Sestoft L
Biochim Biophys Acta. 1980 Nov 17;633(1):56-67. doi: 10.1016/0304-4165(80)90037-9.
The regulation of ketogenesis and gluconeogenesis was studied in isolated, perfused livers from hyper- and euthyroid rats. Experimental conditions were varied with respect to lactate and fatty acid concentration in the perfusion medium and with respect to the nutritional state of the rats. 1. The rate of uptake of oleate in perfused livers was independent of the thyroid and nutritional states of the animals. 2. In livers from 48-h-fasted rats no difference was found in rates of ketogenesis between the euthyroid and hyperthyroid livers except when 10 mM lactate was present in the perfusate. In recently fed rats the rates of ketogenesis from oleate (1 mM) and endogenous substrates were low in euthyroid livers (0.45 and 0.05 mumol/min per g liver, respectively), while these rates in hyperthyroid livers were (1.333 and 0.136 mumol/min per g liver, respectively). With octanoate as substrate, high rates of ketogenesis were found in recently fed livers from both euthyroid and hyperthyroid rats (1.573 and 1.717 mumol/min per g liver, respectively). 3. Without oleate in the perfusion medium the rate of gluconeogenesis from low (1 mM) lactate concentrations in livers from 48 h-fasted-rats was slightly increased in the hyperthyroid state (0.548 mumol/min per g liver) compared to the euthyroid state (0.408 mumol/min per g liver). When lactate concentration in the perfusion medium was raised to 10 mM the rate of gluconeogenesis was increased 4-fold in the hyperthyroid livers (1.800 mumol/min per g liver) but only 20% in the euthyroid livers (0.490 mumol/min per g liver). The presence of oleate (1 mM) had no effect on the rate of gluconeogenesis from low lactate concentrations in livers form 48-h-fasted animals of either thyroid state. At 10 mM lactate the inclusion of oleate caused a pronounced stimulation of gluconeogenesis in euthyroid livers (from 0.490 to 1.766 mumol/min per g liver) but not in hyperthyroid livers (from 1.800 to 1.973 mumol/min per g liver) so that the difference in the rate of gluconeogenesis between the two thyroid states disappeared. 4. The content of endogenous substrates was measured in liver biopsies taken before perfusion. The glycogen concentration was independent of the thyroid state in 48-h fasted animals. The triglyceride content was independent of the thyroid state in recently fed animals. In recently fed animals the glycogen content was reduced by 90% in hyperthyroid animals, and in 48-h-fasted animals the triglyceride content was reduced by 50% in hyperthyroid animals. 5. The energy cost of gluconeogenesis from lactate appeared to be independent of the thyroid state.
在甲状腺功能亢进和甲状腺功能正常的大鼠离体灌注肝脏中研究了生酮作用和糖异生作用的调节。实验条件在灌注介质中的乳酸和脂肪酸浓度以及大鼠的营养状态方面有所不同。1. 灌注肝脏中油酸的摄取速率与动物的甲状腺和营养状态无关。2. 在禁食48小时的大鼠肝脏中，甲状腺功能正常和甲状腺功能亢进的肝脏生酮速率没有差异，除非灌注液中存在10 mM乳酸。在近期喂食的大鼠中，甲状腺功能正常的肝脏中油酸（1 mM）和内源性底物的生酮速率较低（分别为每克肝脏0.45和0.05 μmol/分钟），而甲状腺功能亢进的肝脏中的这些速率分别为（每克肝脏1.333和0.136 μmol/分钟）。以辛酸为底物时，在甲状腺功能正常和甲状腺功能亢进的近期喂食大鼠肝脏中均发现高生酮速率（分别为每克肝脏1.573和1.717 μmol/分钟）。3. 在灌注介质中没有油酸的情况下，与甲状腺功能正常的状态（每克肝脏0.408 μmol/分钟）相比，甲状腺功能亢进状态下禁食48小时大鼠肝脏中低（1 mM）乳酸浓度的糖异生速率略有增加（每克肝脏0.548 μmol/分钟）。当灌注介质中的乳酸浓度升至10 mM时，甲状腺功能亢进肝脏中的糖异生速率增加了4倍（每克肝脏1.800 μmol/分钟），而甲状腺功能正常的肝脏中仅增加了20%（每克肝脏0.490 μmol/分钟）。油酸（1 mM）的存在对两种甲状腺状态的禁食48小时动物肝脏中低乳酸浓度的糖异生速率没有影响。在10 mM乳酸时，加入油酸会导致甲状腺功能正常的肝脏中糖异生明显刺激（从每克肝脏0.490增加到1.766 μmol/分钟），但在甲状腺功能亢进的肝脏中没有（从每克肝脏1.800增加到1.973 μmol/分钟），因此两种甲状腺状态之间的糖异生速率差异消失。4. 在灌注前采集的肝脏活检中测量内源性底物的含量。禁食48小时的动物中糖原浓度与甲状腺状态无关。近期喂食的动物中甘油三酯含量与甲状腺状态无关。在近期喂食的动物中，甲状腺功能亢进动物的糖原含量降低了90%，在禁食48小时的动物中，甲状腺功能亢进动物的甘油三酯含量降低了50%。5. 乳酸糖异生的能量消耗似乎与甲状腺状态无关。
