Zinc stimulates glucose consumption by modulating the insulin signaling pathway in L6 myotubes: essential roles of Akt-GLUT4, GSK3β and mTOR-S6K1.
The present study was performed to evaluate the insulin-like effects of zinc in normal L6 myotubes as well as its ability to alleviate insulin resistance. Glucose consumption was measured in both normal and insulin-resistant L6 myotubes. Western blotting and immunofluorescence revealed that zinc exhibited insulin-like glucose transporting effects by activating key markers that are involved in the insulin signaling cascade (including Akt, GLUT4 and GSK3β), and downregulating members of the insulin signaling feedback cascade such as mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K1). In normal L6 myotubes, zinc enhanced glucose consumption via a mechanism that might involve the activation of Akt phosphorylation, glucose transporter 4 (GLUT4) translocation and GSK3β phosphorylation. In contrast, zinc exerted insulin-mimetic effects in insulin-resistant L6 myotubes by upregulating Akt phosphorylation, GLUT4 translocation and GSK3β phosphorylation, and downregulating the expression of mTOR and S6K1. In conclusion, zinc might enhance glucose consumption by modulating insulin signaling pathways including Akt-GLUT4, GSK3β, mTOR and S6K1.
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China. Electronic address: Wuyuntang@tmu.edu.cn.
Yuntang
Y
Wu
Tanggu Centers for Disease Control and Prevention, Tianjin Binhai New Area,Tianjin, China.
Huizi
H
Lu
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
Huijun
H
Yang
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
Chunlei
C
Li
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
Qian
Q
Sang
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
Xinyan
X
Liu
Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin, China.
Yongzhe
Y
Liu
Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin, China.
Yongming
Y
Wang
Department of Epidemiology and biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
Zhong
Z
Sun
D065567:Absorption, Physiological; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D019587:Dietary Supplements; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000819:agonists* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000737:chemistry / Q000378:metabolism*; D007333:Insulin Resistance; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D015415:Biomarkers; D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; C546845:mTOR protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; C526901:Rps6kb1 protein, rat; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; D015032:Zinc
Akt; GSK3β; Glucose consumption; Insulin signaling pathway; L6 myotubes; Zinc; mTOR