title: The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling.
abstract: Transmembrane protein 18 (TMEM18) is an ill-described, obesity-related gene, but few studies have explored its molecular function. We found single-nucleotide polymorphism data, suggesting that TMEM18 may be involved in the regulation/physiology of metabolic syndrome based on associations with insulin, homeostatic model assessment-β (HOMAβ), triglycerides, and blood sugar. We then found an ortholog in the Drosophila genome, knocked down Drosophila Tmem18 specifically in insulin-producing cells, and tested for its effects on metabolic function. Our results suggest that TMEM18 affects substrate levels through insulin and glucagon signaling, and its downregulation induces a metabolic state resembling type 2 diabetes. This work is the first to experimentally describe the metabolic consequences of TMEM18 knockdown, and further supports its association with obesity.
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden lyle.wiemerslage@neuro.uu.se.
authors.forename: Lyle
authors.initials: L
authors.lastname: Wiemerslage
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Priya A
authors.initials: PA
authors.lastname: Gohel
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Giulia
authors.initials: G
authors.lastname: Maestri
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Torfi G
authors.initials: TG
authors.lastname: Hilmarsson
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Michel
authors.initials: M
authors.lastname: Mickael
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: Department of NeuroscienceFunctional Pharmacology, Uppsala University, Uppsala, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005216:Fat Body / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007814:Larva / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D008565:Membrane Proteins; C530715:TMEM18 protein, human; D005934:Glucagon
keywords: AKH; CG30051; Drosophila; SNP; TMEM18; fly; glucagon; insulin; obesity