Wiemerslage, L., Gohel, P.A., Maestri, G., Hilmarsson, T.G., Mickael, M., Fredriksson, R., Williams, M.J., Schiöth, H.B. (2016). The Drosophila ortholog of TMEM18 regulates insulin and glucagon-like signaling.  J. Endocrinol. 229(3): 233--243.

FBrf0232712

Research paper

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.