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KPNβ1 promotes palmitate-induced insulin resistance via NF-κB signaling in hepatocytes

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Abstract

It has been intensively studied that inflammation contributes to the insulin resistance development in obesity-induced type 2 diabetes mellitus (T2DM). In this study, we assessed the effect of karyopherin β1 (KPNβ1) in hepatic insulin resistance and the underlying mechanisms using high-fat diet (HFD) fed mice and palmitate (PA)-stimulated hepatocytes (HepG2). KPNβ1 expression is increased in the HFD fed mice liver. PA upregulated KPNβ1 expression in HepG2 cells in a time-dependent manner. PA also increased pro-inflammatory cytokines expression, including tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β). KPNβ1 knockdown reversed PA-induced pro-inflammatory cytokines expression and insulin-stimulated glucose uptake in HepG2 cells. In addition, KPNβ1 knockdown reduced intracellular lipid accumulation. Mechanistically, KPNβ1 transports nuclear factor kB (NF-κB) p65 from the cytoplasm to the nucleus to increase pro-inflammatory genes expression. In summary, KPNβ1 acts as a positive regulator in the NF-κB pathway to enhance palmitate-induced inflammation response and insulin resistance in HepG2 cells.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, XiSi Road 20, Nantong, 226001, China

    Suxin Wang, Yun Zhao, Nana Xia, Wanlu Zhang, Zhuqi Tang, Cuifang Wang, Xiaohui Zhu & Shiwei Cui

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  1. Suxin Wang
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  2. Yun Zhao
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  3. Nana Xia
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  4. Wanlu Zhang
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  5. Zhuqi Tang
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  6. Cuifang Wang
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  7. Xiaohui Zhu
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  8. Shiwei Cui
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Corresponding author

Correspondence to Shiwei Cui.

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All procedures involving animals were approved by the Experimental Animal Center of Nantong University.

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The authors declare that they have no competing interests.

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Wang, S., Zhao, Y., Xia, N. et al. KPNβ1 promotes palmitate-induced insulin resistance via NF-κB signaling in hepatocytes. J Physiol Biochem 71, 763–772 (2015). https://doi.org/10.1007/s13105-015-0440-x

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  • DOI: https://doi.org/10.1007/s13105-015-0440-x

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