title: The Stimulatory Effect of Essential Fatty Acids on Glucose Uptake Involves Both Akt and AMPK Activation in C2C12 Skeletal Muscle Cells.
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.
authors: 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.
authors: So Yeon
authors: SY
authors: Park
authors: Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors: Min Hye
authors: MH
authors: Kim
authors: Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors: Joung Hoon
authors: JH
authors: Ahn
authors: Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors: Su Jin
authors: SJ
authors: Lee
authors: Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors: Jong Ho
authors: JH
authors: Lee
authors: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
authors: Won Sik
authors: WS
authors: Eum
authors: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
authors: Soo Young
authors: SY
authors: Choi
authors: Department of Physiology, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors: Hyeok Yil
authors: HY
authors: Kwon
keywords: AMPK; C2C12 cells; Essential fatty acid; Glucose uptake; Insulin signaling