In vivo Metabolic Imaging of Insulin with Multiphoton Fluorescence of Human Insulin–Au Nanodots

Authors

  • Chien-Liang Liu,

    1. Department of Chemistry, National Taiwan University, Taipei, 10617 Taiwan, Fax: +886-2-369-5208
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  • Tzu-Ming Liu,

    Corresponding author
    1. Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan, Fax: +886-2-2394-0049
    2. Molecular Imaging Center, National Taiwan University, Taipei 10617, Taiwan
    • Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan, Fax: +886-2-2394-0049.
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  • Tsung-Yuan Hsieh,

    1. Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan, Fax: +886-2-2394-0049
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  • Han-Wen Liu,

    1. Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan, Fax: +886-2-2394-0049
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  • Yu-Shing Chen,

    1. Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan, Fax: +886-2-2394-0049
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  • Cheng-Kun Tsai,

    1. Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan, Fax: +886-2-2394-0049
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  • Hsieh-Chih Chen,

    1. Department of Chemistry, National Taiwan University, Taipei, 10617 Taiwan, Fax: +886-2-369-5208
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  • Jong-Wei Lin,

    1. Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 10002, Taiwan
    2. Cardiovascular Center and Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin county 64041, Taiwan
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  • Ron-Bin Hsu,

    1. Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan
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  • Tzung-Dau Wang,

    1. Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei 10002, Taiwan
    2. Cardiovascular Center and Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin county 64041, Taiwan
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  • Chien-Cheng Chen,

    1. Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei 10617, Taiwan
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  • Chi-Kuang Sun,

    1. Molecular Imaging Center, National Taiwan University, Taipei 10617, Taiwan
    2. Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei 10617, Taiwan
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  • Pi-Tai Chou

    Corresponding author
    1. Department of Chemistry, National Taiwan University, Taipei, 10617 Taiwan, Fax: +886-2-369-5208
    • Department of Chemistry, National Taiwan University, Taipei, 10617 Taiwan, Fax: +886-2-369-5208
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Abstract

Functional human insulin–Au nanodots (NDs) are synthesized for the in vivo imaging of insulin metabolism. Benefiting from its efficient red to near infrared fluorescence, deep tissue subcellular uptake of insulin–Au NDs can be clearly resolved through a least-invasive harmonic generation and two-photon fluorescence (TPF) microscope. In vivo investigations on mice ear and ex vivo assays on human fat tissues conclude that cells with rich insulin receptors have higher uptake of administrated insulin. Interestingly, the insulin–Au NDs can even permeate into lipid droplets (LDs) of adipocytes. Using this newly discovered metabolic phenomenon of insulin, it is found that enlarged adipocytes in type II diabetes mice have higher adjacent/LD concentration contrast with small-sized ones in wild type mice. For human clinical samples, the epicardial adipocytes of patients with diabetes and coronary artery disease (CAD) also show elevated adjacent/LD concentration contrast. As a result, human insulin–Au nanodots provide a new approach to explore subcellular insulin metabolism in model animals or patients with metabolic or cardiovascular diseases.

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