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Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes

Author

Listed:
  • Biliana Marcheva

    (Northwestern University Feinberg School of Medicine
    Northwestern University)

  • Kathryn Moynihan Ramsey

    (Northwestern University Feinberg School of Medicine
    Northwestern University)

  • Ethan D. Buhr

    (Northwestern University)

  • Yumiko Kobayashi

    (Northwestern University Feinberg School of Medicine
    Northwestern University)

  • Hong Su

    (Molecular Biology and Cell Biology, Northwestern University)

  • Caroline H. Ko

    (Northwestern University)

  • Ganka Ivanova

    (Northwestern University Feinberg School of Medicine
    Northwestern University)

  • Chiaki Omura

    (Northwestern University Feinberg School of Medicine
    Northwestern University)

  • Shelley Mo

    (Weinberg College of Arts and Sciences, Northwestern University)

  • Martha H. Vitaterna

    (Center for Sleep and Circadian Biology, Northwestern University)

  • James P. Lopez

    (University of Chicago)

  • Louis H. Philipson

    (University of Chicago)

  • Christopher A. Bradfield

    (McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health)

  • Seth D. Crosby

    (Washington University School of Medicine)

  • Lellean JeBailey

    (GeneGo Inc.)

  • Xiaozhong Wang

    (Molecular Biology and Cell Biology, Northwestern University)

  • Joseph S. Takahashi

    (University of Texas Southwestern Medical Center
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center)

  • Joseph Bass

    (Northwestern University Feinberg School of Medicine
    Northwestern University
    Center for Sleep and Circadian Biology, Northwestern University)

Abstract

Clocking on to diabetes During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis — a rhythmic process that is disturbed in people with diabetes. Experiments in mice now show that the pancreatic islets contain their own biological clock, which orchestrates insulin secretion during the sleep–wake cycle. The transcription factors CLOCK and BMAL1 are vital for this process, and mice with defective copies of the genes Clock and Bmal1 develop hypoinsulinaemia and diabetes. By demonstrating that a local tissue clock integrates circadian and metabolic signals in pancreatic β-cells, this work suggests that circadian analyses are crucial for deeper understanding of metabolic phenotypes, as well as for the treatment of metabolic diseases such as type 2 diabetes.

Suggested Citation

  • Biliana Marcheva & Kathryn Moynihan Ramsey & Ethan D. Buhr & Yumiko Kobayashi & Hong Su & Caroline H. Ko & Ganka Ivanova & Chiaki Omura & Shelley Mo & Martha H. Vitaterna & James P. Lopez & Louis H. P, 2010. "Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes," Nature, Nature, vol. 466(7306), pages 627-631, July.
  • Handle: RePEc:nat:nature:v:466:y:2010:i:7306:d:10.1038_nature09253
    DOI: 10.1038/nature09253
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    Cited by:

    1. M Ann Kelly & Simon D Rees & M Zafar I Hydrie & A Samad Shera & Srikanth Bellary & J Paul O’Hare & Sudhesh Kumar & Shahrad Taheri & Abdul Basit & Anthony H Barnett & DIAGRAM consortium & SAT2D consort, 2012. "Circadian Gene Variants and Susceptibility to Type 2 Diabetes: A Pilot Study," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-7, April.
    2. Samuel E Jones & Jessica Tyrrell & Andrew R Wood & Robin N Beaumont & Katherine S Ruth & Marcus A Tuke & Hanieh Yaghootkar & Youna Hu & Maris Teder-Laving & Caroline Hayward & Till Roenneberg & James , 2016. "Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci," PLOS Genetics, Public Library of Science, vol. 12(8), pages 1-19, August.
    3. Chuntao Zhang & Yan Tu & Tao Ma & Qiyu Diao, 2022. "Connection between Circadian Rhythm and Rumen Digestibility of Concentrate and Roughage in Sheep," Agriculture, MDPI, vol. 12(12), pages 1-13, December.
    4. Li Lin & Ciyong Lu & Weiqing Chen & Vivian Yawei Guo, 2021. "Daytime Napping and Nighttime Sleep Duration with Incident Diabetes Mellitus: A Cohort Study in Chinese Older Adults," IJERPH, MDPI, vol. 18(9), pages 1-13, May.
    5. Peter C St. John & Francis J Doyle III, 2015. "Quantifying Stochastic Noise in Cultured Circadian Reporter Cells," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-17, November.

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