Oncotarget

Research Papers:

Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes

Sha Tao, Qi Yuan, Li Mao _, Feng-Li Chen, Feng Ji and Zhao-Hui Cui

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Oncotarget. 2017; 8:67605-67613. https://doi.org/10.18632/oncotarget.18754

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Abstract

Sha Tao1,*, Qi Yuan1,*, Li Mao1, Feng-Li Chen2, Feng Ji3 and Zhao-Hui Cui1

1Department of Endocrinology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

2Clinical Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

3Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China

*These authors are considered as co-first authors

Correspondence to:

Li Mao, email: hamaoliys@163.com

Feng Ji, email: huaiaifengjidr@163.com

Keywords: vitamin D, insulin resistance, oxidative stress, hepatocytes, N-acetylcysteine (NAC)

Received: April 21, 2017     Accepted: May 23, 2017     Published: June 28, 2017

ABSTRACT

Vitamin D deficiency could cause insulin resistance. However, the underlying mechanisms are unclear. The 1α-Hydroxylase [“1α(OH)ase”] is a key enzyme for activate vitamin D3 synthesis. Here, we show that 1α(OH)ase stable knockdown by targeted shRNA led to vitamin D3 depletion in L02 hepatocytes. 1α(OH)ase silence also inhibited insulin-induced downstream signaling (IRS-1, ERK and AKT) transduction and glucose transporter 4 expression. Further, 1α(OH)ase shRNA in L02 hepatocytes led to significant reactive oxygen species production, p53-p21 activation and DNA damages. Such effects were almost completely reversed with co-treatment of n-acetylcysteine, which is an established anti-oxidant. Remarkably, insulin-induced downstream signaling transduction and glucose transporter 4 expression were recovered with n-acetylcysteine co-treatment in 1α(OH)ase-silenced L02 hepatocytes. Together, our results suggest that vitamin D deficiency-induced insulin resistance is possibly caused by oxidative stress in hepatocytes.


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