Exploration of the molecular mechanism of insulin resistance in adipose tissue of patients with type 2 diabetes mellitus through a bioinformatic analysis.

Abstract

Background: We aimed to determine the cis-expression Quantitative Trait Loci (cis-eQTL) and trans-eQTL of differentially expressed genes (DEGs) in insulin resistance (IR) related pathways.

Methods: The expression profile data for insulin sensitivity (IS) and IR in the adipose tissue of patients with type 2 diabetes mellitus (T2DM) were acquired from the Gene Expression Omnibus databases. Then, the Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) methods were performed to identify the significant enrichment of potential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between IS and IR groups, and the Wilcoxon rank sum test was carried out to identify the DEGs related to KEGG pathways. Finally, the cis-eQTLs and trans-eQTLs that can affect the expression of DEGs were screened from the eQTLGen database.

Results: The GSEA and GSVA analysis indicated that the mTOR signaling pathway, insulin signaling pathway and T2DM had a strong correlation with the pathological process of T2DM. Furthermore, six genes (ACACA, GYS2, PCK1, PRKAR1A, SLC2A4, and VEGFA) were found to be significantly differentially expressed in IR-related pathways. Finally, we have identified a total of 1073 cis-eQTLs and 24 trans-eQTLs.

Conclusions: We screened out six genes that were significantly differentially expressed in IR-related pathways, including ACACA, GYS2, PCK1, PRKAR1A, SLC2A4, and VEGFA. Moreover, we discovered that these six genes were affected by 1073 cis-eQTLs and 24 trans-eQTLs.