Sugano T, Shiota M, Tanaka T, Miyamae Y, Shimada M, Oshino N
J Biochem. 1980 Jan;87(1):153-66. doi: 10.1093/oxfordjournals.jbchem.a132721.
The role of the cellular redox state in the hormonal stimulation of gluconeogenesis was studied in hemoglobin-free perfused rat liver, by fluorimetric measurement of the redox states of intracellular pyridine nucleotides. The maximum rate of glucose production from lactate/pyruvate mixture was observed with a lactate/pyruvate ratio of 10/1, which corresponds to the ratio observed in vivo. Increased reduction of pyridine nucleotides on infusion of ethanol or octanoate was associated with an increased production of glucose from pyruvate, whereas glucose production from lactate decreased. Stimulation of gluconeogenesis from lactate by glucagon was affected by the lactate/pyruvate ratio; a decrease of the lactate/pyruvate ratio resulted in a decrease of the efficacy of glucagon. Stimulation by glucagon of glucose production from pyruvate was abolished during octanoate infusion, although it was still observable during ethanol infusion. In contrast to glucagon, the stimulatory effect of norepinephrine on gluconeogenesis was unaffected by the ratio of lactate to pyruvate. Norepinephrine in the presence of octanoate and ethanol still induced stimulation of glucose production from lactate and pyruvate, which was always accompanied by a transient reduction of pyridine nucleotides. The results demonstrate that the regeneration of NADH in the cytosol is one of the regulatory factors in gluconeogenesis, and that the effects of glucagon and norepinephrine on gluconeogenesis and on the redox state of pyridine nucleotides are not identical.
通过荧光法测定细胞内吡啶核苷酸的氧化还原状态，在无血红蛋白灌注的大鼠肝脏中研究了细胞氧化还原状态在激素刺激糖异生中的作用。观察到乳酸/丙酮酸混合物产生葡萄糖的最大速率时，乳酸/丙酮酸的比例为10/1，这与体内观察到的比例相对应。输注乙醇或辛酸后吡啶核苷酸还原增加，与丙酮酸生成葡萄糖增加相关，而乳酸生成葡萄糖减少。胰高血糖素对乳酸糖异生的刺激受乳酸/丙酮酸比例的影响；乳酸/丙酮酸比例降低导致胰高血糖素的效力降低。输注辛酸期间，胰高血糖素对丙酮酸生成葡萄糖的刺激作用消失，尽管在输注乙醇期间仍可观察到。与胰高血糖素不同，去甲肾上腺素对糖异生的刺激作用不受乳酸与丙酮酸比例的影响。在有辛酸和乙醇存在的情况下，去甲肾上腺素仍能刺激乳酸和丙酮酸生成葡萄糖，这总是伴随着吡啶核苷酸的短暂还原。结果表明，胞质溶胶中NADH的再生是糖异生的调节因子之一，并且胰高血糖素和去甲肾上腺素对糖异生和吡啶核苷酸氧化还原状态的影响并不相同。
