• glucose metabolism disease

The Drosophila Dgk gene was isolated in an RNAi screen for neuronal genes involved in energy homeostasis and obesity. Using a GAL4 neuronal driver specific to late pupal and adult stages, RNAi lines exhibiting significant changes in triglyceride levels in an initial screen were characterized further. Dmel\Dgk is orthologous to three genes in human, DGKB, DGKG, and DGKA. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Dgk.

The human genes DGKB and DGKG have been associated with metabolic phenotypes of various types in GWAS studies, including type II diabetes mellitus, fasting blood glucose measurement, body mass index, and weight. Hsap\DGKG and Hsap\DGKA have been introduced into flies, but have not been characterized. DGKB has not been introduced into flies.

Knockdown, via RNAi, of neuronal Dmel\Dgk levels in late pupal and adult stages results in increased triglyceride, glucose, and glycogen levels. Knockdown specifically in the insulin-producing cells (IPCs), a set of neurosecretory neurons in the brain, results in the same phenotypes. Experiments support a model that the Dgk protein impacts levels of circulating insulin-like peptides at the level of secretion from the IPCs.

[updated Jul. 2019 by FlyBase; FBrf0222196]