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

Rupali Ugrankar; Eric Berglund; Fatih Akdemir; Christopher Tran; Min Soo Kim; Jungsik Noh; Rebekka Schneider; Benjamin Ebert; Jonathan M. Graff

doi:10.1038/ncomms8102

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

Rupali Ugrankar, Eric Berglund, Fatih Akdemir, Christopher Tran, Min Soo Kim, Jungsik Noh, Rebekka Schneider, Benjamin Ebert, Jonathan M. Graff

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64 Scopus citations

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.

Original language	English (US)
Article number	7102
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8102
State	Published - May 21 2015

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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.",

author = "Rupali Ugrankar and Eric Berglund and Fatih Akdemir and Christopher Tran and Kim, {Min Soo} and Jungsik Noh and Rebekka Schneider and Benjamin Ebert and Graff, {Jonathan M.}",

note = "Funding Information: We are grateful to Drs David Mangelsdorf and Steven Kliewer for use of equipment. We thank the Bloomington Stock Center for fly stocks and the UT Southwestern Mouse Metabolic Phenotyping Core (MMPC). We are also grateful to members of the Graff lab for support, reagents and insights. We thank Benjamin Ebert, Harvard University, for kindly gifting us the CSNK1a1 conditional knockout mice. This study was supported by the National Institute of Health and the National Institute of Diabetes and Digestive and Kidney Disease grants (R01 DK066556, R01 DK064261 and R01 DK088220) to J.M.G., and by the American Diabetes Association grant (7-12-MN-23) to J.G. and R.U.",

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AU - Kim, Min Soo

AU - Noh, Jungsik

AU - Schneider, Rebekka

AU - Ebert, Benjamin

AU - Graff, Jonathan M.

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

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