Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5504428 | Archives of Biochemistry and Biophysics | 2017 | 30 Pages |
Abstract
This study examined the hypothesis that vitamin-D prevents oxidative stress and upregulates glucose metabolism via activating insulin-independent signaling molecules in 3T3-L1 adipocytes and in high fat diet (HFD)-fed mice. To investigate the mechanism 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) (0-50 nM). Results showed that 1,25(OH)2D3 supplementation decreased NOX4 expression, ROS production, NF-κB phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells. 1,25(OH)2D3 supplementation upregulated SIRT1 expression and AMPK phosphorylation and stimulated the IRS1/PI3K/PIP3/AKT/PKCζ signaling cascade, GLUT4 expression, and glucose uptake in HG-treated adipocytes. The effect of 1,25(OH)2D3 on the phosphorylation of both AMPK and IRS1, GLUT4 expression, and glucose uptake was significantly inhibited in SIRT1-knockdown adipocytes. This suggests the role of insulin-independent signaling molecules (SIRT1, AMPK) in mediating the effect of 1,25(OH)2D3 on the signaling cascade of glucose uptake. In addition, cholecalciferol supplementation significantly upregulated pAMPK, SIRT-1 and GLUT-4 levels in adipose tissue of mice fed with HFD. This study demonstrates a novel molecular mechanism by which vitamin-D can prevent oxidative stress and upregulates glucose uptake via SIRT1/AMPK/IRS1/GLUT4 cascade in HG-treated adipocytes and in adipose tissue of HFD diabetic mice.
Keywords
Sirt1PTP1BIRS1PIP3VDRNOX4sirtuin 1TrxGLUT4GLUT1AMPKNrf2NF-κBPI3K1,25(OH)2D31,25-dihydroxyvitamin D3AMP activated protein kinaseAktOxidative stressthioredoxinglucose transporter 4insulin receptor substrate 1nuclear factor erythroid 2-related factor 2nuclear factor kappa Bphosphatase and tensin homologphosphatidylinositol-3,4,5-trisphosphatephosphoinositide 3-kinaseGlucose metabolismVitamin DProtein tyrosine phosphatase 1BSerine/threonine protein kinasePtenglucose transporter 1high glucoseinsulin receptorVitamin D receptor
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Authors
Prasenjit Manna, Arunkumar E. Achari, Sushil K. Jain,