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Betel nut extract and arecoline block insulin signaling and lipid storage in 3T3-L1 adipocytes

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Abstract

According to several population-based studies, betel nut chewing is associated with metabolic syndrome and diabetes in British South Asians and Taiwanese. However, the underlying molecular mechanism is not yet clear. Arecoline is an alkaloid-type natural product found in betel nuts. Our aim was to clarify the influence of betel nut extract and arecoline on lipid accumulation and insulin signaling in adipocytes. We found that betel nut extract and arecoline blocked lipid storage in 3T3-L1 adipocytes. The possible mechanism may function by inhibiting the expression of the insulin receptor, glucose transporter-4, fatty acid synthase, and the lipid droplet proteins perilipin and adipophilin. In addition, betel nut extract and arecoline increased the basal level of IRS-1 serine307 phosphorylation and decreased insulin-stimulated IRS-1 tyrosine, Akt, and PI3 kinase phosphorylation. In conclusion, betel nut extract and arecoline have diabetogenic potential on adipocytes that may result in insulin resistance and diabetes at least in part via the obstruction of insulin signaling and the blockage of lipid storage.

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Acknowledgments

This work was supported by grants from the Center of Excellence for Environmental Medicine (KMU-EM-97-1.3.f) and the Medical Research Fund (QM094009 and QM094011) of Kaohsiung Medical University, Taiwan, Republic of China. We also thank Elsevier’s Webshop for the language editing.

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Authors and Affiliations

  1. Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan, Republic of China

    Tusty-Jiuan Hsieh, Wei-Chiao Chang & Shyi-Jang Shin

  2. Graduate Institute of Occupational Safety and Health, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan, Republic of China

    Pei-Chen Hsieh & Ming-Tsang Wu

  3. Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan, Republic of China

    Ming-Tsang Wu

  4. Center of Environmental and Occupational Medicine, Kaohsiung Municipal Hsia-Kang Hospital, 482 Shan-Ming Road, Kaohsiung, 812, Taiwan, Republic of China

    Ming-Tsang Wu

  5. Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan, Republic of China

    Pi-Jung Hsiao, Kun-Der Lin, Pong-Chun Chou & Shyi-Jang Shin

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  1. Tusty-Jiuan Hsieh
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Hsieh, TJ., Hsieh, PC., Wu, MT. et al. Betel nut extract and arecoline block insulin signaling and lipid storage in 3T3-L1 adipocytes. Cell Biol Toxicol 27, 397–411 (2011). https://doi.org/10.1007/s10565-011-9195-5

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