title: Use of Drosophila as an evaluation method reveals imp as a candidate gene for type 2 diabetes in rat locus Niddm22.
abstract: Type 2 diabetes (T2D) is one of the most common human diseases. QTL analysis of the diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats has identified numerous hyperglycemic loci. However, molecular characterization and/or gene identification largely remains to be elucidated due mostly to the weak genetic variances contributed by each locus. Here we utilized Drosophila melanogaster as a secondary model organism for functional evaluation of the candidate gene. We demonstrate that the tissue specific knockdown of a homologue of igf2bp2 RNA binding protein leads to increased sugar levels similar to that found in the OLETF rat. In the mutant, the expression of two of the insulin-like peptides encoded in the fly genome, dilp2 and dilp3, were found to be downregulated. Consistent with previous reports of dilp mutants, the imp mutant flies exhibited an extension of life span; in contrast, starvation tolerance was reduced. These results further reinforce the possibility that imp is involved in sugar metabolism by modulating insulin expression.
authors.affiliation: Division of Natural Sciences, Department of Life Science, International Christian University, Mitaka, Tokyo 181-8585, Japan.
authors.forename: Kurenai
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Division of Natural Sciences, Department of Life Science, International Christian University, Mitaka, Tokyo 181-8585, Japan.
authors.forename: Sawaka
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Natural Sciences, Department of Life Science, International Christian University, Mitaka, Tokyo 181-8585, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Ogata
authors.affiliation: Division of Natural Sciences, Department of Life Science, International Christian University, Mitaka, Tokyo 181-8585, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of Natural Sciences, Department of Life Science, International Christian University, Mitaka, Tokyo 181-8585, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Takahama
authors.affiliation: Laboratory of Animal Genetics, Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan.
authors.forename: Takahisa
authors.identifier: 0000-0003-2800-4989
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Natural Sciences, Department of Life Science, International Christian University, Mitaka, Tokyo 181-8585, Japan.
authors.forename: Hiroyuki
authors.identifier: 0000-0001-9462-0873
authors.initials: H
authors.lastname: Kose
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D034622:RNA Interference; D051381:Rats; D020334:Rats, Inbred OLETF
chemical_list: D001786:Blood Glucose; D029721:Drosophila Proteins; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D049452:Green Fluorescent Proteins
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