Qi Ge1, Fan Feng2, Lanlan Liu3, Liang Chen3, Peng Lv3, Shangshang Ma3, Keping Chen4, Qin Yao5. 1. School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. 2. The Fourth Affiliated Hospital of Jiangsu University, 20# Zhengdong Road, Zhenjiang, Jiangsu 212001, PR China. 3. Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. 4. Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: kpchen@ujs.edu.cn. 5. School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: yaoqin@ujs.edu.cn.
Abstract
OBJECTIVE: Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The liver is a key organ involved in glucose metabolism, and the major target proteins' changes in the pathogenesis are still unknown. METHODS: A diabetic mouse model was induced by intraperitoneal injection of streptozotocin (STZ) solution and the RNA-Seq analysis was used to evaluate the transcription differences in the livers of diabetic mice of this study. And then, the differentially expressed genes were validated between a normal mouse group (n = 6) and a diabetic mouse group (n = 6) using quantitative real-time PCR (qRT-PCR) and Western blotting analysis. In addition, we also constructed protein-protein interacting (PPI) networks of up-regulated and down-regulated genes. RESULTS: Transcriptome sequencing analysis revealed 370 up-regulated differentially expressed genes and 281 down-regulated differentially expressed genes in the diabetes model. The gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results showed that the differentially expressed genes were mainly involved in immunity, enzyme activity, metabolism, and steroid synthesis. PPI analysis results indicated that the main 15 core differential proteins (Cyp51a1, Acsl4, Ugt1a1, Stat1, Gsta2, Cbr1, Aldh1a1, Fasn, Ces1, Camk2b, Tap1, Egr1, Sqle, Lpin1, Fabp5) were involved in the pathogenesis of diabetes. The qRT-PCR results showed that expression changes of four genes (Acsl4, Stat1, Gsta2, Fabp5) were in different directions from those of RNA-Seq. Western blotting results indicated that Sqle expression change at the protein level was in opposition direction from qRT-PCR, and we speculated that Sqle may be involved in the post-transcriptional modification process. CONCLUSIONS: Our data speculated that the pathogenesis of diabetes may be mediated mainly through steroid biosynthesis, metabolic processes, and immune responses. Further researches on these pathways may provide new targets for the prevention and treatment of diabetes.
OBJECTIVE:Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The liver is a key organ involved in glucose metabolism, and the major target proteins' changes in the pathogenesis are still unknown. METHODS: A diabeticmouse model was induced by intraperitoneal injection of streptozotocin (STZ) solution and the RNA-Seq analysis was used to evaluate the transcription differences in the livers of diabeticmice of this study. And then, the differentially expressed genes were validated between a normal mouse group (n = 6) and a diabeticmouse group (n = 6) using quantitative real-time PCR (qRT-PCR) and Western blotting analysis. In addition, we also constructed protein-protein interacting (PPI) networks of up-regulated and down-regulated genes. RESULTS: Transcriptome sequencing analysis revealed 370 up-regulated differentially expressed genes and 281 down-regulated differentially expressed genes in the diabetes model. The gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results showed that the differentially expressed genes were mainly involved in immunity, enzyme activity, metabolism, and steroid synthesis. PPI analysis results indicated that the main 15 core differential proteins (Cyp51a1, Acsl4, Ugt1a1, Stat1, Gsta2, Cbr1, Aldh1a1, Fasn, Ces1, Camk2b, Tap1, Egr1, Sqle, Lpin1, Fabp5) were involved in the pathogenesis of diabetes. The qRT-PCR results showed that expression changes of four genes (Acsl4, Stat1, Gsta2, Fabp5) were in different directions from those of RNA-Seq. Western blotting results indicated that Sqle expression change at the protein level was in opposition direction from qRT-PCR, and we speculated that Sqle may be involved in the post-transcriptional modification process. CONCLUSIONS: Our data speculated that the pathogenesis of diabetes may be mediated mainly through steroid biosynthesis, metabolic processes, and immune responses. Further researches on these pathways may provide new targets for the prevention and treatment of diabetes.
Authors: Amanda E Bries; Joe L Webb; Brooke Vogel; Claudia Carrillo; Timothy A Day; Michael J Kimber; Rudy J Valentine; Matthew J Rowling; Stephanie Clark; Kevin L Schalinske; Elizabeth M McNeill Journal: Front Nutr Date: 2021-05-10