期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 615, 期 -, 页码 22-34出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2017.01.002
关键词
High glucose; Oxidative stress; Vitamin D; SIRT1/AMPK/IRS1/GLUT4; Glucose metabolism
资金
- NCCIH [R01 AT00742]
- Malcolm Feist Endowed Chair in Diabetes
- Malcolm Feist Cardiovascular Research Endowment, LSU Health Sciences Center, Shreveport
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)(2)D-3 (1,25-dihydroxyvitamin D-3) (0-50 nM). Results showed that 1,25(OH)(2)D-3 supplementation decreased NOX4 expression, ROS production, NF-kappa B phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells. 1,25(OH)(2)D-3 supplementation upregulated SIRT1 expression and AMPK phosphorylation and stimulated the IRS1/PI3K/PIP3/AKT/PIC zeta signaling cascade, GLUT4 expression, and glucose uptake in HG-treated adipocytes. The effect of 1,25(OH)(2)D-3 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)(2)D-3 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. (C) 2017 Published by Elsevier Inc.
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