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Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development

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Listed:
  • Jayakrishna Ambati

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Joseph Magagnoli

    (Dorn Research Institute, Columbia VA Health Care System
    University of South Carolina)

  • Hannah Leung

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Shao-bin Wang

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Chris A. Andrews

    (University of Michigan Medical School
    University of Michigan)

  • Dongxu Fu

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Akshat Pandey

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Srabani Sahu

    (University of Virginia School of Medicine)

  • Siddharth Narendran

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Shuichiro Hirahara

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Shinichi Fukuda

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Tsukuba)

  • Jian Sun

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Lekha Pandya

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Meenakshi Ambati

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Felipe Pereira

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Akhil Varshney

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Tammy Cummings

    (Dorn Research Institute, Columbia VA Health Care System
    University of South Carolina)

  • James W. Hardin

    (University of South Carolina)

  • Babatunde Edun

    (Dorn Research Institute, Columbia VA Health Care System
    Department of Medicine, Baystate Medical Center)

  • Charles L. Bennett

    (Dorn Research Institute, Columbia VA Health Care System
    University of South Carolina
    University of South Carolina)

  • Kameshwari Ambati

    (University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Benjamin J. Fowler

    (University of Kentucky)

  • Nagaraj Kerur

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine)

  • Christian Röver

    (University Medical Center Göttingen)

  • Norbert Leitinger

    (University of Virginia School of Medicine)

  • Brian C. Werner

    (University of Virginia School of Medicine)

  • Joshua D. Stein

    (University of South Carolina
    University of Michigan Medical School
    University of Michigan School of Public Health)

  • S. Scott Sutton

    (Dorn Research Institute, Columbia VA Health Care System
    University of South Carolina)

  • Bradley D. Gelfand

    (University of Virginia School of Medicine
    University of Virginia School of Medicine
    University of Virginia School of Medicine)

Abstract

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P

Suggested Citation

  • Jayakrishna Ambati & Joseph Magagnoli & Hannah Leung & Shao-bin Wang & Chris A. Andrews & Dongxu Fu & Akshat Pandey & Srabani Sahu & Siddharth Narendran & Shuichiro Hirahara & Shinichi Fukuda & Jian S, 2020. "Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18528-z
    DOI: 10.1038/s41467-020-18528-z
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