title: Attenuation of high sucrose diet-induced insulin resistance in tryptophan 2,3-dioxygenase deficient Drosophila melanogaster vermilion mutants.
abstract: Exposure to high sugar diet (HSD) serves as an experimental model of insulin resistance (IR) and type 2 diabetes (T2D) in mammals and insects. Peripheral IR induced by HSD delays emergence of pupae from larvae and decreases body weight of Drosophila imago. Understanding of mechanisms of IR/T2D is essential for refining T2D prevention and treatment strategies. Dysregulation of tryptophan (TRP) - kynurenine (KYN) pathway was suggested as one of the mechanisms of IR development. Rate-limiting enzyme of TRP - KYN pathway in Drosophila is TRP 2,3-dioxygenase (TDO), an evolutionary conserved ortholog of human TDO. In insects TDO is encoded by vermilion gene. TDO is not active in vermilion mutants. In order to evaluate the possible impact of deficient formation of KYN from TRP on the inducement of IR by HSD, we compared the effect of HSD in wild type (Oregon) and vermilion mutants of Drosophila melanogaster by assessing the time of white pupae emergence from larva and body weight of imago. Delay of emergence of pupae from larvae induced by high sucrose diet was less pronounced in vermilion (1.4 days) than in Oregon flies (3.3 days) in comparison with flies maintained on standard diet. Exposure to high sucrose diet decreased body weight of Oregon (but not vermilion) imago. Attenuation of high sucrose diet-induced IR/T2D in vermilion flies might depend on deficiency of TRP - KYN pathway. Besides IR/T2D, HSD induces obesity in Drosophila. Future studies of HSD-induced obesity and IR/T2D in TDO deficient vermilion mutants of Drosophila might help to understand the mechanisms of high association between IR/T2D and obesity. Modulation of TRP - KYN metabolism might be utilized for prevention and treatment of IR/T2D.
authors.affiliation: Department of Genetics and Cytology, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Navrotskaya
authors.affiliation: Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University/Tufts Medical Center, Boston, MA, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Oxenkrug
authors.affiliation: Department of Genetics and Cytology, V.N. Karazin Kharkiv National University, Kharkiv, Ukraine.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Vorobyova
authors.affiliation: Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University/Tufts Medical Center, Boston, MA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Summergrad
keywords: drosophila; high sugar diet; insulin resistance; kynurenine; obesity; tryptophan; type 2 diabetes