Abdel-aleem S, Li X, Anstadt M P, Perez-Tamayo R A, Lowe J E
Duke University Medical Center, Department of Surgery, Durham, North Carolina.
Horm Metab Res. 1994 Feb;26(2):88-91. doi: 10.1055/s-2007-1000779.
The study of the regulation of glucose utilization by inhibition of fatty acid oxidation is greatly enhanced by the availability of specific inhibitors of fatty acid oxidation. This study examines the regulation of cardiac glucose utilization by inhibition of fatty acid oxidation at different sites. The effects of Etomoxir and 4-bromocrotonic acid (4-BCA) on the oxidation of [1-14C]palmitate, [1-14C]-octanoate and [U-14C]glucose were studied in isolated rat myocytes. Fifty percent inhibition of palmitate oxidation was achieved at 8 microM Etomoxir and 40 microM 4-BCA. Octanoate oxidation was inhibited only by 4-BCA. In contrast to their effect on palmitate oxidation, these inhibitors significantly stimulated the oxidation of glucose in a concentration-dependent manner. Moreover, the oxidation of [2-14C]pyruvate was increased two-fold by these compounds. The rate of utilization of [U-14C]-2-deoxyglucose was also stimulated 2-3 times by these inhibitors. These studies suggest that the stimulation of glucose utilization via the inhibition of fatty acid oxidation may be mediated through the stimulation of both glucose transport and the oxidation of pyruvate by the pyruvate dehydrogenase complex.
脂肪酸氧化特异性抑制剂的可得性极大地促进了通过抑制脂肪酸氧化来研究葡萄糖利用调节的工作。本研究在不同位点通过抑制脂肪酸氧化来考察心脏葡萄糖利用的调节。在分离的大鼠心肌细胞中研究了依托莫司和4-溴巴豆酸（4-BCA）对[1-14C]棕榈酸、[1-14C]辛酸和[U-14C]葡萄糖氧化的影响。在8微摩尔依托莫司和40微摩尔4-BCA时，棕榈酸氧化被抑制了50%。辛酸氧化仅被4-BCA抑制。与它们对棕榈酸氧化的作用相反，这些抑制剂以浓度依赖的方式显著刺激了葡萄糖的氧化。此外，这些化合物使[2-14C]丙酮酸的氧化增加了两倍。这些抑制剂还使[U-14C]-2-脱氧葡萄糖的利用速率提高了2至3倍。这些研究表明，通过抑制脂肪酸氧化来刺激葡萄糖利用可能是通过刺激葡萄糖转运以及丙酮酸脱氢酶复合体对丙酮酸的氧化来介导的。
