Proteomic and bioinformatic analysis of membrane proteome in type 2 diabetic mouse liver

Authors

  • Gun-Hwa Kim,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
    2. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
    3. Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Republic of Korea
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    • These authors contributed equally to this work.

  • Edmond Changkyun Park,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
    2. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
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    • These authors contributed equally to this work.

  • Sung-Ho Yun,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Yeonhee Hong,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
    2. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Dong-Gyu Lee,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
    2. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Eun-Young Shin,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
    2. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
    3. Department of Functional Genomics, University of Science and Technology (UST), Daejeon, Republic of Korea
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  • Jongsun Jung,

    1. Syntekabio Inc, Korea Institute of Science and Technology, Seoul, Republic of Korea
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  • Young Hwan Kim,

    1. Division of Mass Spectrometry Research, Korea Basic Science Institute, Ochang, Republic of Korea
    2. Graduate School of Analytical Science and Technology (GLAST), Chungnam National University, Daejeon, Republic of Korea
    3. Department of Bio-Analytical Science, University of Science and Technology (UST), Daejeon, Republic of Korea
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  • Kyung-Bok Lee,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
    2. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Ik-Soon Jang,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Zee-Won Lee,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
    2. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Young-Ho Chung,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Jong-Soon Choi,

    1. Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Chaejoon Cheong,

    1. Division of Magnetic Resonance Research, Korea Basic Science Institute, Ochang, Republic of Korea
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  • Soohyun Kim,

    Corresponding author
    1. Pioneer Research Center for Protein Network Exploration, Korea Basic Science Institute, Daejeon, Republic of Korea
    • Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Seung Il Kim

    Corresponding author
    1. Department of Bio-Analytical Science, University of Science and Technology (UST), Daejeon, Republic of Korea
    • Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea
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  • Colour Online: See the article online to view Figs. 1, 2, 4, and 6–8 in colour.

Correspondence: Dr. Seung Il Kim, Division of Life Science, Korea Basic Science Institute, 169-148 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea

E-mail: ksi@kbsi.re.kr

Fax: +82-42-865-3419

Additional corresponding author: Dr. Soohyun Kim,

E-mail: shkim@kbsi.re.kr

Abstract

Type 2 diabetes mellitus (T2DM) is the most prevalent and serious metabolic disease affecting people worldwide. T2DM results from insulin resistance of the liver, muscle, and adipose tissue. In this study, we used proteomic and bioinformatic methodologies to identify novel hepatic membrane proteins that are related to the development of hepatic insulin resistance, steatosis, and T2DM. Using FT-ICR MS, we identified 95 significantly differentially expressed proteins in the membrane fraction of normal and T2DM db/db mouse liver. These proteins are primarily involved in energy metabolism pathways, molecular transport, and cellular signaling, and many of them have not previously been reported in diabetic studies. Bioinformatic analysis revealed that 16 proteins may be related to the regulation of insulin signaling in the liver. In addition, six proteins are associated with energy stress-induced, nine proteins with inflammatory stress-induced, and 14 proteins with endoplasmic reticulum stress-induced hepatic insulin resistance. Moreover, we identified 19 proteins that may regulate hepatic insulin resistance in a c-Jun amino-terminal kinase-dependent manner. In addition, three proteins, 14–3-3 protein beta (YWHAB), Slc2a4 (GLUT4), and Dlg4 (PSD-95), are discovered by comprehensive bioinformatic analysis, which have correlations with several proteins identified by proteomics approach. The newly identified proteins in T2DM should provide additional insight into the development and pathophysiology of hepatic steatosis and insulin resistance, and they may serve as useful diagnostic markers and/or therapeutic targets for these diseases.

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