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: Jong Gab Jung, Sung-E Choi, Yoon-Jung Hwang, Sang-A Lee, Eun Kyoung Kim, Min-Seok Lee, Seung Jin Han, Hae Jin Kim, Dae Jung Kim, Yup Kang, Kwan-Woo Lee
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 345 Issue 1-2 Pg. 79-87 (Oct 15 2011) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 21802492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Chemical References

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

Topics

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