Genome-scale transcriptional analysis reveals key genes associated with the development of type II diabetes in mice

Abstract

Abstract. Diabetes mellitus is one of the primary diseases that pose a threat to human health. The focus of the present study is type II diabetes (T2D), which is caused by obesity and is the most prevalent type of diabetes. However, genome-scale transcriptional analysis of diabetic liver in the development process of T2D is yet to be further elucidated. Microassays were performed on liver tissue samples from three-, six-and nine-week-old db/db mice with diabetes and db/m mice to investigate differentially expressed mRNA. Based on the results of genome-scale transcriptional analysis, five genes were screened in the present study: chromobox 8 (CBX8), de-etiolated homolog 1 and damage specific DNA binding protein 1 associated 1 (DDA1), Phosphoinositide-3-kinase regulatory subunit 6 (PIK3R6), WD repeat domain 41 (WDR41) and Glycine Amidinotransferase (GATM). At three weeks of age, no significant differences in levels or ratios of expression were observed. However, at six and nine weeks, expression of CBX8, DDA1, PIK3R6 and WDR41 was significantly upregulated (P<0.05) in the db/db model group compared with the control group, whereas GATM expression was significantly downregulated (P<0.05). These results suggest that T2D-related differential expression of genes becomes more marked with age, which was confirmed via reverse transcription-quantitative polymerase chain reaction. Genome-scale transcriptional analysis in diabetic mice provided a novel insight into the molecular. events associated with the role of mRNAs in T2D development, with specific emphasis upon CBX8, DDA1, PIK3R6, GATM and WDR41. The results of the present study may provide rationale for the investigation of the target genes of these mRNAs in future studies.

Function, Regulation and Biological Roles of PI3Kγ Variants

“…Little is known about the impact of the non-catalytic PI3Kγ subunits in diabetes mellitus (DM). Recently, p87 was reported to be one of the key genes in murine liver tissue associated with the development of type II DM [188], whereas computational analysis suggest that the human p101 belong to a group of highly disordered proteins related to type II DM [189]; however, nothing is known about the relevance of these findings.…”

Comprehensive Transcriptomic Analysis of Critical RNA Regulation Associated With Metabolism and Prognosis in Clear Cell Renal Carcinoma

“…A recent study by Fang et al (2018) showed that there is abnormal metabolism of lipids and fatty acids during gastrointestinal tumor metabolism. Phosphoinositide-3-kinase regulatory subunit 6 (PIK3R6) has been shown to be upregulated in the diabetes rat model, which was associated with the development of type II diabetes in mice ( Zhang et al, 2017 ). Moreover, PIK3R6 has been demonstrated to promote the proliferative and migratory potentials in ovarian cancer cells ( Liu et al, 2020 ).…”

Hepatic gene expression explains primary drug toxicity in bipolar disorder

“…DHTKD1 , involved in lysine metabolism, was shown to reduce mitochondrial activity upon inhibition and might influence the development of diabetes 40 . Likewise, reduced GATM expression levels were indicated to affect the development of diabetes in a murine diabetes model 41 . This leads to the assumption that BPD individuals with psychotropic drug treatment seem to be more prone to develop diabetes compared to controls with resembling liver injury.…”