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JAB1 promotes palmitate-induced insulin resistance via ERK pathway in hepatocytes

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Abstract

Insulin resistance (IR) is the primary pathological mechanism underlying Type 2 diabetes mellitus (T2DM). Many researches have reported the relationship between chronic inflammation and IR, while the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway is rapidly activated in inflammatory conditions. However, the functional role of ERK1/2 in IR remains to be identified. We here reported that C-Jun activation domain-binding protein-1 (JAB1) was upregulated in IR. In addition, we showed that depletion of JAB1 led to recovery of insulin sensitivity. Given the fact that JAB1 played as an activator of ERK1/2, we assumed JAB1 was involved in IR through ERK pathway. So we assessed the effects of JAB1 knockdown in palmitate acid (PA) treated HepG2 cells. Importantly, JAB1 siRNA blocked the effect of PA-induced activation of ERK1/2. Furthermore, silencing of JAB1 could reduce the release of inflammatory factors, facilitate hepatic glucose uptake and improve lipid metabolism. All these data implicated that JAB1 knockdown might alleviate PA-induced IR through ERK pathway in hepatocytes.

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Funding

This work was funded by Suzhou Science and Education Project (No. kjxw2018036) and Science and Technology Development Fund of Nanjing Medical University (NMUB2018218).

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Author notes

  1. Yun Zhao and Suxian Ma contributed equally to this work.

Authors and Affiliations

  1. The Affiliated Suzhou Hospital of Nanjing Medical University, 242 Guangji Road, Suzhou, Jiangsu, 215008, People’s Republic of China

    Yun Zhao, Suxian Ma, Xingna Hu, Min Feng, Rong Xiang, Min Li, Chenxiao Liu, Ting Lu, Aijie Huang, Jiaqi Chen, Mian Wu & Honghong Lu

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  1. Yun Zhao
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  2. Suxian Ma
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  12. Honghong Lu
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Correspondence to Honghong Lu.

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Key Points

• JAB1 plays a role in chronic inflammation.

• JAB1 knockdown has a protective effect on insulin sensitivity.

• We associate JAB1, ERK pathway with insulin resistance.

• JAB1 may act as a possible target for the treatment of T2DM.

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Zhao, Y., Ma, S., Hu, X. et al. JAB1 promotes palmitate-induced insulin resistance via ERK pathway in hepatocytes. J Physiol Biochem 76, 655–662 (2020). https://doi.org/10.1007/s13105-020-00770-0

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  • DOI: https://doi.org/10.1007/s13105-020-00770-0

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