Patel T B, Olson M S
Biochim Biophys Acta. 1986 Oct 10;888(3):316-24. doi: 10.1016/0167-4889(86)90231-4.
The effects of glucagon and the alpha-adrenergic agonist, phenylephrine, on the rate of 14CO2 production and gluconeogenesis from [1-14C]lactate and [1-14C]pyruvate were investigated in isolated perfused livers of 24-h-fasted rats. Both glucagon and phenylephrine stimulated the rate of 14CO2 production from [1-14C]lactate but not from [1-14C]pyruvate. Neither glucagon nor phenylephrine affected the activation state of the pyruvate dehydrogenase complex in perfused livers derived from 24-h-fasted rats. 3-Mercaptopicolinate, an inhibitor of the phosphoenolpyruvate carboxykinase reaction, inhibited the rates of 14CO2 production and glucose production from [1-14C]lactate by 50% and 100%, respectively. Furthermore, 3-mercaptopicolinate blocked the glucagon- and phenylephrine-stimulated 14CO2 production from [1-14C]lactate. Additionally, measurements of the specific radioactivity of glucose synthesized from [1-14C]lactate, [1-14C]pyruvate and [2-14C]pyruvate indicated that the 14C-labeled carboxyl groups of oxaloacetate synthesized from 1-14C-labeled precursors were completely randomized and pyruvate----oxaloacetate----pyruvate substrate cycle activity was minimal. The present study also demonstrates that glucagon and phenylephrine stimulation of the rate of 14CO2 production from [1-14C]lactate is a result of increased metabolic flux through the phosphoenolpyruvate carboxykinase reaction, and phenylephrine-stimulated gluconeogenesis from pyruvate is regulated at step(s) between phosphoenolpyruvate and glucose.
在禁食24小时大鼠的离体灌注肝脏中，研究了胰高血糖素和α-肾上腺素能激动剂去氧肾上腺素对[1-¹⁴C]乳酸和[1-¹⁴C]丙酮酸生成¹⁴CO₂的速率以及糖异生的影响。胰高血糖素和去氧肾上腺素均刺激了[1-¹⁴C]乳酸生成¹⁴CO₂的速率，但未刺激[1-¹⁴C]丙酮酸生成¹⁴CO₂的速率。胰高血糖素和去氧肾上腺素均未影响禁食24小时大鼠灌注肝脏中丙酮酸脱氢酶复合体的激活状态。磷酸烯醇式丙酮酸羧激酶反应的抑制剂3-巯基吡啶甲酸分别使[1-¹⁴C]乳酸生成¹⁴CO₂的速率和葡萄糖生成速率降低了50%和100%。此外，3-巯基吡啶甲酸阻断了胰高血糖素和去氧肾上腺素刺激的[1-¹⁴C]乳酸生成¹⁴CO₂的过程。另外，对由[1-¹⁴C]乳酸、[1-¹⁴C]丙酮酸和[2-¹⁴C]丙酮酸合成的葡萄糖的比放射性测量表明，由1-¹⁴C标记前体合成的草酰乙酸的¹⁴C标记羧基完全随机化，丙酮酸→草酰乙酸→丙酮酸底物循环活性最小。本研究还表明，胰高血糖素和去氧肾上腺素刺激[1-¹⁴C]乳酸生成¹⁴CO₂的速率是磷酸烯醇式丙酮酸羧激酶反应代谢通量增加的结果，而去氧肾上腺素刺激的丙酮酸糖异生在磷酸烯醇式丙酮酸和葡萄糖之间的步骤受到调节。
