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Berberine activates bitter taste responses of enteroendocrine STC-1 cells

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Abstract

Glucagon-like peptide-1 (GLP-1) is involved in the regulation of insulin secretion and glucose homeostasis. GLP-1 release is stimulated when berberine interacts with a novel G protein family (TAS2Rs) in enteroendocrine cells. In this study, we used STC-1 cells and examined a marked increase in Ca2+ in response to various bitter compounds. Ca2+ responses to traditional Chinese medicine extracts, including berberine, phellodendrine and coptisine, in STC-1 cells were suppressed by the phospholipase C (PLC) inhibitor U-73122, suggesting the involvement of bitter taste receptors in changing the physiological status of enteroendocrine cells in a PLC-dependent manner. STC-1 cells showed berberine-up-regulated preproglucagon (GLP-1 precursor) mRNA and GLP-1 secretion. A QPCR analysis demonstrated that TAS2R38, a subtype of the bitter taste receptor, was associated with GLP-1 secretion. Berberine-mediated GLP-1 secretion was attenuated in response to small interfering RNA silencing of TAS2R38. The current studies demonstrated that Gα-gustducin co-localized with GLP-1 and Tas2r106 in the STC-1 cells. We further utilized inhibitors of PLC and TRPM5, which are known to participate in taste signal transduction, to investigate the underlying pathways mediated in berberine-induced GLP-1 secretion. Berberine-induced GLP-1 release from enteroendocrine cells is modulated in a PLC-dependent manner through a process involving the activation of bitter taste receptors. Together, our data demonstrated a berberine-mediated GLP-1 secretion pathway in mouse enteroendocrine cells that could be of therapeutic relevance to hyperglycemia and the role of bitter taste receptors in the function of the small intestine.

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Acknowledgements

The present study was supported by the Chinese National Natural Science Foundation (Grant Nos. 31571171and 31100838), the Shanghai Natural Science Foundation (Grant No.15ZR1414900), the Key Laboratory of Medical Electrophysiology (Southwest Medical University) of Ministry of Education of China (Grant No. 201502), and the Young Teachers of Shanghai Universities Training Program. The authors thank Shenghui Xing and Qian Li for their selfless help.

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  1. Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, 200444, People’s Republic of China

    Xiao Yue, Jie Liang, Fu Gu, Dongshu Du & Fuxue Chen

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  1. Xiao Yue
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Yue, X., Liang, J., Gu, F. et al. Berberine activates bitter taste responses of enteroendocrine STC-1 cells. Mol Cell Biochem 447, 21–32 (2018). https://doi.org/10.1007/s11010-018-3290-3

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