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Molecular and Cellular Endocrinology

Volume 345, Issues 1–2, 15 October 2011, Pages 79-87345 (1-2), 79-87

2011 Oct 15

Supplementation of Pyruvate Prevents Palmitate-Induced Impairment of Glucose Uptake in C2 Myotubes

Jong Gab Jung 1Sung-E ChoiYoon-Jung HwangSang-A LeeEun Kyoung KimMin-Seok LeeSeung Jin HanHae Jin KimDae Jung KimYup KangKwan-Woo Lee

Abstract

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.

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