title: Drosophila glucome screening identifies Ck1alpha as a regulator of mammalian glucose metabolism.
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.
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Rupali
authors.initials: R
authors.lastname: Ugrankar
authors.affiliation: 1] Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Berglund
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Fatih
authors.initials: F
authors.lastname: Akdemir
authors.affiliation: 1] Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] University of Texas, Dallas, Texas 75080, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Tran
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Jungsik
authors.initials: J
authors.lastname: Noh
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ebert
authors.affiliation: 1] Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Graff
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D050260:Carbohydrate Metabolism; D047389:Casein Kinase I / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D005216:Fat Body / Q000378:metabolism; D005260:Female; D059647:Gene-Environment Interaction; D005947:Glucose / Q000378:metabolism*; D006458:Hemolymph / Q000378:metabolism; D006943:Hyperglycemia / Q000235:genetics*; D008297:Male; D055442:Metabolome; D051379:Mice; D009132:Muscles / Q000201:enzymology; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014199:Trehalose / Q000378:metabolism
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014199:Trehalose; D047389:Casein Kinase I; D005947:Glucose