SRA

We showed in this present study that HSD feeding could induce type 2 diabetes-like phenotype in fruit flies, resembling the key disease features including hyperglycemia, glucosuria, increased hunger and thirsty, unexplained weight loss, and reduced female fecundity. We also showed that HSD-fed flies shared similar molecular mechanisms underlying type 2 diabetes patients, including both insulin deficiency and insulin resistance. Last but not least, disrupting insulin signaling in fruit flies could mimic the effect of HSD feeding to induce type 2 diabetes-like phenotype, further confirming that these phenotypes were a result of compromised insulin signaling upon HSD feeding. Taken together, we demonstrated that this diet-induced type 2 diabetes model in fruit flies rightly and comprehensively recapitulated the physiological, metabolic, behavioral, and molecular features of human type 2 diabetes, offering a valid and accessible model to study the underlying mechanism of this disease and to validate potential diagnostics and therapeutic tools. Given the highly conserved regulatory framework of physiology and metabolism between flies and human, our work has paved a way to generate novel insights into type 2 diabetes, a common, severe, and yet poorly understood disease in human. Overall design: Total RNA from fly brains or fat body was extracted from 5-day-old female flies using the RNeasy Mini kit (Qiagen, Germany), subjected to poly(A) mRNA isolation, cDNA synthesization, library preparation (NEBNext Ultra RNA Library Prep Kit, NEB), and sequencing (Illumina Hiseq X Ten). Sequence data were subsequently mapped to Drosophila genome and uniquely mapped reads were collected for further analysis. Gene expression was calculated by the RPKM (Reads Per Kilobase of exon per Million reads mapped). The genes with p-value less 0.05 and fold change more than 1 were considered as the differentially expressed gene.