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Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

Authors
Jung, JG; Choi, SE; Hwang, YJ; Lee, SA; Kim, EK; Lee, MS; Han, SJ; Kim, HJ; Kim, DJ; Kang, Y; Lee, KW
Citation
Molecular and cellular endocrinology, 345(1-2):79-87, 2011
Journal Title
Molecular and cellular endocrinology
ISSN
0303-72071872-8057
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.
MeSH terms
AnimalsCitric Acid Cycle/drug effectsGene Expression RegulationGlucose/*metabolismGlucose Transporter Type 4/genetics/metabolismIntracellular Space/drug effects/metabolismMiceMuscle Fibers, Skeletal/*drug effects/enzymology/*metabolismOxidation-Reduction/drug effectsPalmitic Acid/*pharmacologyPhosphorylation/drug effectsProto-Oncogene Proteins c-akt/metabolismPyruvates/*pharmacologyRNA, Messenger/genetics/metabolism
DOI
10.1016/j.mce.2011.07.023
PMID
21802492
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 민석한, 승진김, 혜진김, 대중강, 엽이, 관우
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