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The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
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2016 (English)In: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 229, no 3, 233-243 p.Article in journal (Refereed) PublishedText
Abstract [en]

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-beta (HOMA beta), 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.

Place, publisher, year, edition, pages
2016. Vol. 229, no 3, 233-243 p.
Keyword [en]
Drosophila, fly, insulin, obesity, SNP, TMEM18, CG30051, glucagon, AKH
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-300572DOI: 10.1530/JOE-16-0040ISI: 000379384500007PubMedID: 27029472OAI: oai:DiVA.org:uu-300572DiVA: diva2:951661
Funder
Swedish Research Council
Available from: 2016-08-09 Created: 2016-08-09 Last updated: 2016-08-09Bibliographically approved

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Wiemerslage, LyleFredriksson, RobertWilliams, Michael J.Schiöth, Helgi B.
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Functional PharmacologyDepartment of Pharmaceutical Biosciences
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