Ciprés G, Urcelay E, Butta N, Ayuso M S, Parrilla R, Martín-Requero A
Centro de Investigaciones Biológicas, Madrid, Spain.
Am J Physiol. 1994 Oct;267(4 Pt 1):E528-36. doi: 10.1152/ajpendo.1994.267.4.E528.
This work aimed to determine the role played by the adrenal gland in the fatty acid control of gluconeogenesis in isolated perfused rat livers. The gluconeogenic substrate concentration responses were not altered in adrenalectomized (ADX) rats. This observation indicates that glucocorticoids are not essential to maintain normal basal gluconeogenic rates. In contrast, fatty acid failed to stimulate gluconeogenesis from lactate and elicited attenuated stimulation with pyruvate as substrate in livers from ADX rats. Fatty acid-induced stimulation of respiration and ketone body production were similar in control and ADX rats. Thus the diminished responsiveness of the gluconeogenic pathway to fatty acid cannot be the result of different rates of energy production and/or generation of reducing power. Fatty acids did not inhibit pyruvate decarboxylation in livers from ADX rats. Even though mitochondria isolated from livers of ADX rats showed normal basal rates of pyruvate metabolism, fatty acids failed to inhibit pyruvate decarboxylation and the activity of the pyruvate dehydrogenase complex. This novel observation of the glucocorticoid effect in controlling the pyruvate dehydrogenase complex responsiveness indicates that the mitochondrial partitioning of pyruvate between carboxylation and decarboxylation reactions may be altered in livers from ADX rats. We propose that the diminished effect of fatty acid in stimulating gluconeogenesis in livers from ADX rats is the result of a limited pyruvate availability for the carboxylase reaction due to a lack of inhibition of flux through the pyruvate dehydrogenase complex.
这项研究旨在确定肾上腺在离体灌注大鼠肝脏中脂肪酸对糖异生的调控作用。肾上腺切除（ADX）大鼠的糖异生底物浓度反应未发生改变。这一观察结果表明，糖皮质激素对于维持正常的基础糖异生速率并非必不可少。相反，在ADX大鼠的肝脏中，脂肪酸未能刺激乳酸生成糖异生，且以丙酮酸为底物时引发的刺激减弱。在对照大鼠和ADX大鼠中，脂肪酸诱导的呼吸刺激和酮体生成相似。因此，糖异生途径对脂肪酸反应性降低并非能量产生速率不同和/或还原力生成不同的结果。脂肪酸并未抑制ADX大鼠肝脏中的丙酮酸脱羧反应。尽管从ADX大鼠肝脏分离的线粒体显示丙酮酸代谢的基础速率正常，但脂肪酸未能抑制丙酮酸脱羧反应以及丙酮酸脱氢酶复合体的活性。这一关于糖皮质激素对丙酮酸脱氢酶复合体反应性调控作用的新观察结果表明，在ADX大鼠的肝脏中，丙酮酸在羧化和脱羧反应之间的线粒体分配可能发生了改变。我们认为，ADX大鼠肝脏中脂肪酸刺激糖异生作用减弱是由于丙酮酸脱氢酶复合体通量缺乏抑制，导致羧化酶反应的丙酮酸可用性受限所致。
