title: Using Drosophila to discover mechanisms underlying type 2 diabetes.
abstract: Mechanisms of glucose homeostasis are remarkably well conserved between the fruit flyDrosophila melanogasterand mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. Type 2 diabetes results from insulin insufficiency in the context of ongoing insulin resistance. Although genetic susceptibility is thought to govern the propensity of individuals to develop type 2 diabetes mellitus under appropriate environmental conditions, many of the human genes associated with the disease in genome-wide association studies have not been functionally studied. Recent advances in the phenotyping of metabolic defects have positionedDrosophilaas an excellent model for the functional characterization of large numbers of genes associated with type 2 diabetes mellitus. Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis.
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA Neuroscience Program, Stanford University School of Medicine, Stanford, CA 94305, USA rwalfa@stanford.edu seungkim@stanford.edu.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Alfa
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA Department of Medicine (Oncology), Stanford University School of Medicine, Stanford, CA 94305, USA rwalfa@stanford.edu seungkim@stanford.edu.
authors.forename: Seung K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007328:Insulin; D005947:Glucose
keywords: Diabetes; Drosophila; Insulin resistance; Insulin-like peptides