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.
Highlights
About 344 million people were diagnosed with type 2 diabetes (T2D) worldwide in 2013
In order to evaluate the possible impact of deficient formation of KYN from TRP on the inducement of insulin resistance (IR) by high sugar diet (HSD), we compared the effect of HSD on development of IR in vermilion mutant and wild type (Oregon) Drosophila melanogaster
High sucrose diet delayed pupae emergence from larva of wild type flies (Oregon) in comparison with flies maintained on standard nutrition medium by 3.3 days
Summary
About 344 million people were diagnosed with type 2 diabetes (T2D) worldwide in 2013. In the US about 16 million people have impaired glucose tolerance (pre-diabetes), a high-risk state for T2D: up to 70% of individuals with prediabetes eventually develop T2D [2]. Dysregulation of kynurenine (KYN) pathway of tryptophan (TRP) metabolism (KP) was suggested as one of the mechanisms of development of IR and T2D [37]. Drosophila model allows for further studies of KP involvement in mechanisms of IR/T2D due to availability of natural mutants with deficient KP. 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 on development of IR in vermilion mutant and wild type (Oregon) Drosophila melanogaster
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
