KMEB, Department of Endocrinology, Odense University Hospital, DK-5000 Odense, Denmark.
Biochem Biophys Res Commun. 2010 Jan 15;391(3):1369-73. doi: 10.1016/j.bbrc.2009.12.066. Epub 2009 Dec 21.
To date, two cardinal principles govern oxidation of glucose and fatty acids in skeletal muscle; exogenous fatty acid reduces glucose oxidation and glucose reduces fatty acid oxidation. Both glucose and palmitate (PA) oxidation was increased by increasing their concentration and inhibited by increasing concentrations of the other in human myotubes established from healthy, lean subjects exposed to acute stepwise increases in glucose and PA levels. At high substrate levels; PA oxidation was reduced while release of acid soluble metabolites was increased and, both glucose oxidation and release of citrate was increased which could be abolished by phenylacetic acid (inhibitor of pyruvate carboxylase (PC)). The present data challenges above preconceptions. Although they operate at low-moderate substrate levels additional two principles determine substrate oxidation at higher substrate concentrations; first, anaplerosis of the tricarboxylic cycle through PC promoting complete and incomplete glucose oxidation; second, inhibition of complete PA oxidation with increasing incomplete PA oxidation mediated by high glucose and PA levels, respectively.
迄今为止，有两个基本原则支配着骨骼肌中葡萄糖和脂肪酸的氧化；外源脂肪酸会降低葡萄糖氧化，而葡萄糖会降低脂肪酸氧化。在健康、瘦素的个体中，当葡萄糖和棕榈酸（PA）浓度逐渐增加时，在人肌管中建立的细胞中，两种葡萄糖和 PA 的氧化都增加，而另一种的浓度增加则会受到抑制。在高底物水平下；PA 氧化减少，而可溶酸代谢物的释放增加，葡萄糖氧化和柠檬酸释放增加，而苯乙酸（丙酮酸羧化酶（PC）抑制剂）可消除这种增加。目前的数据挑战了上述先入为主的观念。尽管它们在低中等底物水平下起作用，但在更高的底物浓度下，还有另外两个原则决定了底物的氧化；首先，通过 PC 使三羧酸循环进行氨补反应，促进完全和不完全的葡萄糖氧化；其次，随着高葡萄糖和 PA 水平的增加，完全 PA 氧化受到抑制，而不完全 PA 氧化增加，分别由高葡萄糖和 PA 水平介导。
