title: Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.
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.
authors.affiliation: Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Kyunggi-do, Republic of Korea.
authors.forename: Jong Gab
authors.initials: JG
authors.lastname: Jung
authors.forename: Sung-E
authors.initials: SE
authors.lastname: Choi
authors.forename: Yoon-Jung
authors.initials: YJ
authors.lastname: Hwang
authors.forename: Sang-A
authors.initials: SA
authors.lastname: Lee
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.forename: Min-Seok
authors.initials: MS
authors.lastname: Lee
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Dae Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
authors.forename: Kwan-Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000818:Animals; D002952:Citric Acid Cycle / Q000187:drug effects; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D011773:Pyruvates; D012333:RNA, Messenger; D019308:Palmitic Acid; C104813:methyl pyruvate; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose