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Berberine inhibits gluconeogenesis in spontaneous diabetic rats by regulating the AKT/MAPK/NO/cGMP/PKG signaling pathway

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Abstract

This work was aimed to investigate the action mechanism of berberine (BBR) on gluconeogenesis. The effects of BBR were examined in rat primary hepatocytes and confirmed in vivo in spontaneous diabetic rats. Protein levels were assessed by Western blot. Immunofluorescence staining was utilized for visualizing protein expression, while qRT-PCR helped for the determination of gene expression at the mRNA level. Besides, cGMP concentration was measured using ELISA, whereas NO level was assessed by spectrophotometry. BBR inhibited gluconeogenesis by downregulating G6Pase and PEPCK via inhibition of CREB phosphorylation. Moreover, BBR enhanced NO and cGMP concentrations, leading to the activation of the NO/cGMP/PKG signaling via activating AKT1/MAPK axis. The in vivo experiments were consistent with the findings obtained in vitro. Hence, BBR represents a drug candidate for diabetic patients and its mechanism of action may be driven via the AKT/MAPK/NO/cGMP/PKG pathway.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the Budget projects of Shanghai University of traditional Chinese medicine [Grant Number 18LK063], the Shanghai Key Medical Specialities [Grant Number ZK2019B16] and the Clinical Characteristics of Health System in Putuo District, Shanghai [Grant Number 2020tszk01].

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Author notes

  1. Ming Lu, Yanpeng Wang and Yuanye Jiang have equally contributed to this work and shared first authorship.

Authors and Affiliations

  1. Department of Endocrinology Metabolism, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China

    Ming Lu, Cuiping Zhang, Hongping Wang, Wenjun Sha, Lin Chen & Tao Lei

  2. Department of Endocrinology & Metabolism, Shanghai Putuo District Liqun Hospital, 910 Taopu Road, Shanghai, 200333, China

    Ming Lu

  3. Department of Cardiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China

    Yanpeng Wang

  4. Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200062, China

    Yuanye Jiang

  5. Department of Endocrinology & Metabolism, Shanghai Diabetes Institute, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China

    Limei Liu

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  1. Ming Lu
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Contributions

ML, YW and YJ contributed to the manuscript writing, study design and data analysis. CZ, HW, WS and LC contributed to the drafting of the manuscript. TL and LL supervised the work and designed the study and manuscript writing. All the authors have read and approved the final version to be published.

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Correspondence to Tao Lei or Limei Liu.

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All procedures involving animal studies were carried out with respect to the animal care guidelines and ethical committee approval from Shanghai Putuo Hospital affiliated to Shanghai University of Traditional Chinese Medicine.

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Lu, M., Wang, Y., Jiang, Y. et al. Berberine inhibits gluconeogenesis in spontaneous diabetic rats by regulating the AKT/MAPK/NO/cGMP/PKG signaling pathway. Mol Cell Biochem 478, 2013–2027 (2023). https://doi.org/10.1007/s11010-022-04604-z

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