Human type 2 diabetes mellitus-associated transcriptional disturbances in a high-sugar diet long-term exposed Drosophila melanogaster.

Autor: Loreto JS; Programa de Pós-graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Avenida Roraima, 1000, 97105-900 Santa Maria, RS, Brazil., Ferreira SA; Programa de Pós-graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Avenida Roraima, 1000, 97105-900 Santa Maria, RS, Brazil., Ardisson-Araújo DM; Programa de Pós-graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Avenida Roraima, 1000, 97105-900 Santa Maria, RS, Brazil; Laboratório de Virologia de Insetos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Avenida Roraima, 1000, 97105-900 Santa Maria, RS, Brazil. Electronic address: daniel.araujo@ufsm.br., Barbosa NV; Programa de Pós-graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Avenida Roraima, 1000, 97105-900 Santa Maria, RS, Brazil. Electronic address: nvbarbosa@yahoo.com.br.
Jazyk: angličtina
Zdroj: Comparative biochemistry and physiology. Part D, Genomics & proteomics [Comp Biochem Physiol Part D Genomics Proteomics] 2021 Sep; Vol. 39, pp. 100866. Date of Electronic Publication: 2021 Jun 16.
DOI: 10.1016/j.cbd.2021.100866
Abstrakt: Type 2 Diabetes mellitus (T2DM) is a multifactorial and polygenic disorder with the molecular bases still idiopathic. Experimental analyses and tests are quite limited upon human samples due to the access, variability of patient's conditions, and the size and complexity of the genome. Therefore, high-sugar diet exposure is commonly used for modeling T2DM in non-human animals, which includes invertebrate organisms like the fruit fly Drosophila melanogaster. Interestingly, high-sugar diet (HSD) induces delayed time for pupation and reduced viability in fruit fly larvae hatched from a 30% sucrose-containing medium (HSD-30%). Here we carried out an mRNA-deep sequencing study to identify differentially transcribed genes in adult fruit fly hatched and reared from an HSD-30%. Seven days after hatching, flies reared on control and HSD-30% were used to glucose and triglyceride level measurements and RNA extraction for sequencing. Remarkably, glucose levels were about 2-fold higher than the control group in fruit flies exposed to HSD-30%, whereas triglycerides levels increased 1.7-fold. After RNA-sequencing, we found that 13.5% of the genes were differentially transcribed in the dyslipidemic and hyperglycaemic insects. HSD-30% up-regulated genes involved in ribosomal biogenesis (e.g. dTOR, ERK and dS6K) and down-regulated genes involved in energetic process (e.g. Pfk, Gapdh1, and Pyk from pyruvate metabolism; kdn, Idh and Mdh2 from the citric acid cycle; ATPsynC and ATPsynẞ from ATP synthesis) and insect development. We found a remarkable down-regulation for Actin (Act88F) that likely impairs muscle development. Moreover, HSD-30% up-regulated both the insulin-like peptides 7 and 8 and down-regulated the insulin receptor substrate p53, isoform A and insulin-like peptide 6 genes, whose functional products are insulin signaling markers. All these features pointed together to a tightly correlation of the T2DM-like phenotype modeled by the D. melanogaster and an intricate array of phenomena, which includes energetic processes, muscle development, and ribosomal synthesis as that observed for the human pathology.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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