The Drosophila Ortholog of TMEM18 Regulates Insulin and Glucagon-Like Signaling

J Endocrinol. 2016 Jun;229(3):233-43. doi: 10.1530/JOE-16-0040. Epub 2016 Mar 30.

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.

Keywords: AKH; CG30051; Drosophila; SNP; TMEM18; fly; glucagon; insulin; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Fat Body / metabolism
  • Gene Knockdown Techniques
  • Genes, Insect
  • Glucagon / metabolism*
  • Humans
  • Insulin / metabolism*
  • Larva / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Obesity / genetics
  • Obesity / metabolism
  • Polymorphism, Single Nucleotide
  • Signal Transduction
  • Species Specificity

Substances

  • Drosophila Proteins
  • Insulin
  • Membrane Proteins
  • TMEM18 protein, human
  • Glucagon