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Differential impact of cold and hot tea extracts on tyrosine phosphatases regulating insulin receptor activity: a focus on PTP1B and LMW-PTP

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Abstract

Purpose

The impact of tea constituents on the insulin-signaling pathway as well as their antidiabetic activity are still debated questions. Previous studies suggested that some tea components act as Protein Tyrosine Phosphatase 1B (PTP1B) inhibitors. However, their nature and mechanism of action remain to be clarified. This study aims to evaluate the effects of both tea extracts and some of their constituents on two main negative regulators of the insulin-signaling pathway, Low-Molecular-Weight Protein Tyrosine Phosphatase (LMW-PTP) and PTP1B.

Methods

The effects of cold and hot tea extracts on the enzyme activity were evaluated through in vitro assays. Active components were identified using gas chromatography—mass spectrometry (GC–MS) analysis. Finally, the impact of both whole tea extracts and specific active tea components on the insulin-signaling pathway was evaluated in liver and muscle cells.

Results

We found that both cold and hot tea extracts inhibit LMW-PTP and PTP1B, even if with a different mechanism of action. We identified galloyl moiety-bearing catechins as the tea components responsible for this inhibition. Specifically, kinetic and docking analyses revealed that epigallocatechin gallate (EGCG) is a mixed-type non-competitive inhibitor of PTP1B, showing an IC50 value in the nanomolar range. Finally, in vitro assays confirmed that EGCG acts as an insulin-sensitizing agent and that the chronic treatment of liver cells with tea extracts results in an enhancement of the insulin receptor levels and insulin sensitivity.

Conclusion

Altogether, our data suggest that tea components are able to regulate both protein levels and activation status of the insulin receptor by modulating the activity of PTP1B.

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Acknowledgements

Molecular graphics and analyses were performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311.

Funding

This work was supported by University of Florence and by Associazione Italiana per la Ricerca sul Cancro (AIRC, project “Assaying tumor metabolic deregulation in live cells”, project code 19515).

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Authors and Affiliations

  1. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134, Florence, Italy

    Massimo Genovese, Simone Luti, Elisa Pardella, Mirella Vivoli-Vega, Luigia Pazzagli, Matteo Parri, Anna Caselli, Paolo Cirri & Paolo Paoli

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  1. Massimo Genovese
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  2. Simone Luti
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  3. Elisa Pardella
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Contributions

Conceptualization: LP, PP; methodology: SL, MVV; data curation: MG, MP; formal analysis and investigation: SL, MP, MVV, EP; visualization. EP, AC; writing—original draft preparation: PP; writing—review and editing: all the authors; funding acquisition: PP; resources: AC, LP, PP; supervision: PC, PP.

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Correspondence to Elisa Pardella.

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Genovese, M., Luti, S., Pardella, E. et al. Differential impact of cold and hot tea extracts on tyrosine phosphatases regulating insulin receptor activity: a focus on PTP1B and LMW-PTP. Eur J Nutr 61, 1905–1918 (2022). https://doi.org/10.1007/s00394-021-02776-w

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