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Drosophila glucome screening identifies Ck1alpha as a regulator of mammalian glucose metabolism

Author

Listed:
  • Rupali Ugrankar

    (University of Texas Southwestern Medical Center)

  • Eric Berglund

    (Advanced Imaging Research Center, University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Fatih Akdemir

    (University of Texas Southwestern Medical Center)

  • Christopher Tran

    (University of Texas Southwestern Medical Center
    University of Texas)

  • Min Soo Kim

    (University of Texas Southwestern Medical Center)

  • Jungsik Noh

    (University of Texas Southwestern Medical Center)

  • Rebekka Schneider

    (Brigham and Women's Hospital, Harvard Medical School)

  • Benjamin Ebert

    (Brigham and Women's Hospital, Harvard Medical School)

  • Jonathan M. Graff

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

Abstract

Circulating carbohydrates are an essential energy source, perturbations in which are pathognomonic of various diseases, diabetes being the most prevalent. Yet many of the genes underlying diabetes and its characteristic hyperglycaemia remain elusive. Here we use physiological and genetic interrogations in D. melanogaster to uncover the ‘glucome’, the complete set of genes involved in glucose regulation in flies. Partial genomic screens of ∼1,000 genes yield ∼160 hyperglycaemia ‘flyabetes’ candidates that we classify using fat body- and muscle-specific knockdown and biochemical assays. The results highlight the minor glucose fraction as a physiological indicator of metabolism in Drosophila. The hits uncovered in our screen may have conserved functions in mammalian glucose homeostasis, as heterozygous and homozygous mutants of Ck1alpha in the murine adipose lineage, develop diabetes. Our findings demonstrate that glucose has a role in fly biology and that genetic screenings carried out in flies may increase our understanding of mammalian pathophysiology.

Suggested Citation

  • Rupali Ugrankar & Eric Berglund & Fatih Akdemir & Christopher Tran & Min Soo Kim & Jungsik Noh & Rebekka Schneider & Benjamin Ebert & Jonathan M. Graff, 2015. "Drosophila glucome screening identifies Ck1alpha as a regulator of mammalian glucose metabolism," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8102
    DOI: 10.1038/ncomms8102
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