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Korean J Physiol Pharmacol. 2014 Jun;18(3):255-61. doi: 10.4196/kjpp.2014.18.3.255. Epub 2014 Jun 12.

The Stimulatory Effect of Essential Fatty Acids on Glucose Uptake Involves Both Akt and AMPK Activation in C2C12 Skeletal Muscle Cells.

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology

So Yeon Park, Min Hye Kim, Joung Hoon Ahn, Su Jin Lee, Jong Ho Lee, Won Sik Eum, Soo Young Choi, Hyeok Yil Kwon

Affiliations

  1. Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea. ; Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
  2. Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
  3. Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
  4. Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.

PMID: 24976766 PMCID: PMC4071179 DOI: 10.4196/kjpp.2014.18.3.255

Abstract

Essential fatty acid (EFA) is known to be required for the body to function normally and healthily. However, the effect of EFA on glucose uptake in skeletal muscle has not yet been fully investigated. In this study, we examined the effect of two EFAs, linoleic acid (LA) and α-linolenic acid (ALA), on glucose uptake of C2C12 skeletal muscle cells and investigated the mechanism underlying the stimulatory effect of polyunsaturated EFAs in comparison with monounsaturated oleic acid (OA). In palmitic acid (PA)-induced insulin resistant cells, the co-treatment of EFAs and OA with PA almost restored the PA-induced decrease in the basal and insulin-stimulated 2-NBDG (fluorescent D-glucose analogue) uptake, respectively. Two EFAs and OA significantly protected PA-induced suppression of insulin signaling, respectively, which was confirmed by the increased levels of Akt phosphorylation and serine/threonine kinases (PKCθ and JNK) dephosphorylation in the western blot analysis. In PA-untreated, control cells, the treatment of 500 µM EFA significantly stimulated 2-NBDG uptake, whereas OA did not. Phosphorylation of AMP-activated protein kinase (AMPK) and one of its downstream molecules, acetyl-CoA carboxylase (ACC) was markedly induced by EFA, but not OA. In addition, EFA-stimulated 2-NBDG uptake was significantly inhibited by the pre-treatment of a specific AMPK inhibitor, adenine 9-β-D-arabinofuranoside (araA). These data suggest that the restoration of suppressed insulin signaling at PA-induced insulin resistant condition and AMPK activation are involved at least in the stimulatory effect of EFA on glucose uptake in C2C12 skeletal muscle cells.

Keywords: AMPK; C2C12 cells; Essential fatty acid; Glucose uptake; Insulin signaling

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