Abstract
ObjectivesAlterations in natural killer (NK) cells activity cause damage to pancreatic islets in type 1 diabetes mellitus (T1DM). The aim of this study is to identify T1DM ketosis- or ketoacidosis-related genes in activated CD56+CD16+ NK cells.MethodsMicroarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the GEO2R tool. Enrichment analyses were performed using Metascape online database and GSEA software. Cell-specific gene co-expression network was built using NetworkAnalyst tools. Cytoscape software was used to identify hub genes and construct co-expressed networks. Target miRNAs were predicted based on the DIANA-micro T, miRDB, and miRWalk online databases.ResultsA total of 70 DEGs were identified between T1DM patients recovered from ketosis or ketoacidosis and healthy control blood samples in GSE44314. Among the DEGs, 10 hub genes were screened out. The mature NK cell-specific gene co-expression network for DEGs in T1DM was built using NetworkAnalyst tools. DEGs between activated CD56+CD16+ NK cells and CD56brightCD16- NK cells were identified from GSE1511. After intersection, 13 overlapping genes between GSE44314 and GSE1511 microarray datasets were screened out, in which 7 hub genes were identified. Additionally, 59 target miRNAs were predicted according to the 7 hub genes. After validating with the exosome miRNA expression profile dataset of GSE97123, seven differentially expressed miRNAs (DEmiRNAs) in plasma-derived exosome were selected. Finally, a mRNA–miRNA network was constructed, which was involved in the T1DM ketosis or ketoacidosis process.ConclusionThis work identified seven hub genes in activated CD56+CD16+ NK cells and seven miRNAs in plasma-derived exosome as potential predictors of T1DM ketoacidosis, which provided a novel insight for the pathogenesis at the transcriptome level.
Highlights
Diabetic ketoacidosis (DKA) is one kind of serious acute hyperglycemic complication of type 1 diabetes mellitus (T1DM) [1]
Our study analyzed differentially expressed genes (DEGs) between healthy controls and T1DM who recovered from ketosis or ketoacidosis, as well as the DEGs between activated CD56+CD16+ NK cells and CD56brightCD16NK cells
In order to explore the correlation between T1DM ketone prone and activated CD56+CD16+ NK cells, the intersection of DEGs in the two data series was performed and 13 overlapped genes were screened out
Summary
Diabetic ketoacidosis (DKA) is one kind of serious acute hyperglycemic complication of type 1 diabetes mellitus (T1DM) [1]. DKA can be a preliminary sign of T1DM and is associated with high morbidity and mortality without optimal treatment. The cost of hospital treatment for patients experiencing DKA exceeds the cost of routine treatment for diabetes [2]. The most common causes of DKA include inadequate dose of insulin, infection, intercurrent illness, and drugs [3]. DKA is an initial manifestation of T1DM [4]. Early identification of DKA-related gene expression is of great significance for prevention
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
