Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Kyunggi-do, Republic of Korea.
Mol Cell Endocrinol. 2011 Oct 15;345(1-2):79-87. doi: 10.1016/j.mce.2011.07.023. Epub 2011 Jul 23.
Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and α-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest that pyruvate depletion plays a critical role in PIGR and PIIGU; thus, pyruvate supplementation may help prevent obesity-induced insulin resistance in muscle cells.
脂肪酸水平升高被认为与胰岛素抵抗有关。葡萄糖转运蛋白 4（GLUT4）基因的抑制以及 GLUT4 易位受损可能是脂肪酸引起胰岛素抵抗的介质。本研究旨在确定棕榈酸处理是否抑制 GLUT4 表达，葡萄糖/脂肪酸代谢是否影响棕榈酸诱导的 GLUT4 基因抑制（PIGR），以及是否尝试预防 PIGR 恢复棕榈酸诱导的葡萄糖摄取受损（PIIGU）在 C2 肌管中。不仅脂肪酸氧化的刺激物，如苯扎贝特、AICAR 和 TOFA，而且 TCA 循环底物，如丙酮酸、亮氨酸/谷氨酰胺和 α-酮异己酸/单甲基琥珀酸，都能显著预防 PIGR。特别是通过甲基丙酮酸补充丙酮酸几乎完全防止了 PIIGU，而棕榈酸处理降低了细胞内丙酮酸水平。这些结果表明，丙酮酸耗竭在 PIGR 和 PIIGU 中起着关键作用；因此，丙酮酸补充可能有助于预防肌肉细胞中肥胖引起的胰岛素抵抗。
