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

Mol Cell Endocrinol. 2011 Oct 15;345(1-2):79-87. doi: 10.1016/j.mce.2011.07.023. Epub 2011 Jul 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Citric Acid Cycle / drug effects
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Mice
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / metabolism*
  • Oxidation-Reduction / drug effects
  • Palmitic Acid / pharmacology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyruvates / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Glucose Transporter Type 4
  • Pyruvates
  • RNA, Messenger
  • Palmitic Acid
  • methyl pyruvate
  • Proto-Oncogene Proteins c-akt
  • Glucose