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Journal of Physiology and Biochemistry

, Volume 71, Issue 4, pp 763–772 | Cite as

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

  • Suxin Wang
  • Yun Zhao
  • Nana Xia
  • Wanlu Zhang
  • Zhuqi Tang
  • Cuifang Wang
  • Xiaohui Zhu
  • Shiwei Cui
Original Paper

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.

Keywords

KPNβ1 Inflammation Insulin resistance NF-κB 

Notes

Compliance with ethical standards

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

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© University of Navarra 2015

Authors and Affiliations

  • Suxin Wang
    • 1
  • Yun Zhao
    • 1
  • Nana Xia
    • 1
  • Wanlu Zhang
    • 1
  • Zhuqi Tang
    • 1
  • Cuifang Wang
    • 1
  • Xiaohui Zhu
    • 1
  • Shiwei Cui
    • 1
  1. 1.Department of Endocrinology and Metabolic DiseasesAffiliated Hospital of Nantong UniversityNantongChina

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