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

被引：16

作者：

Wang, Suxin ^{[1
]}

Zhao, Yun ^{[1
]}

Xia, Nana ^{[1
]}

Zhang, Wanlu ^{[1
]}

Tang, Zhuqi ^{[1
]}

Wang, Cuifang ^{[1
]}

Zhu, Xiaohui ^{[1
]}

Cui, Shiwei ^{[1
]}

机构：

[1] Affiliated Hosp Nantong Univ, Dept Endocrinol & Metab Dis, Nantong 226001, Peoples R China

来源：

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY | 2015年 / 71卷 / 04期

关键词：

KPN beta 1; Inflammation; Insulin resistance; NF-kappa B; INFLAMMATORY MECHANISMS; NUCLEAR IMPORT; FATTY-ACIDS; OBESITY; GLUCOSE; INHIBITION; PATHOGENESIS; ACTIVATION; PATHWAYS; STRESS;

D O I：

10.1007/s13105-015-0440-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 beta 1 (KPN beta 1) in hepatic insulin resistance and the underlying mechanisms using high-fat diet (HFD) fed mice and palmitate (PA)-stimulated hepatocytes (HepG2). KPN beta 1 expression is increased in the HFD fed mice liver. PA upregulated KPN beta 1 expression in HepG2 cells in a time-dependent manner. PA also increased pro-inflammatory cytokines expression, including tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 1 beta (IL-1 beta). KPN beta 1 knockdown reversed PA-induced pro-inflammatory cytokines expression and insulin-stimulated glucose uptake in HepG2 cells. In addition, KPN beta 1 knockdown reduced intracellular lipid accumulation. Mechanistically, KPN beta 1 transports nuclear factor kB (NF-kappa B) p65 from the cytoplasm to the nucleus to increase pro-inflammatory genes expression. In summary, KPN beta 1 acts as a positive regulator in the NF-kappa B pathway to enhance palmitate-induced inflammation response and insulin resistance in HepG2 cells.

引用

页码：763 / 772

页数：10

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