Abstract
Insulin resistance is present in the majority of patients with non-insulin-dependent diabetes mellitus (NIDDM) and obesity. In this study, we aimed to investigate the key genes and potential molecular mechanism in insulin resistance. Expression profiles of the genes were extracted from the Gene Expression Omnibus (GEO) database. Pathway and Gene Ontology (GO) enrichment analyses were conducted at Enrichr. The protein–protein interaction (PPI) network was settled and analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database constructed by Cytoscape software. Modules were extracted and identified by the PEWCC1 plugin. The microRNAs (miRNAs) and transcription factors (TFs) which control the expression of differentially expressed genes (DEGs) were analyzed using the NetworkAnalyst algorithm. A database (GSE73108) was downloaded from the GEO databases. Our results identified 873 DEGs (435 up-regulated and 438 down-regulated) genetically associated with insulin resistance. The pathways which were enriched were pathways in complement and coagulation cascades and complement activation for up-regulated DEGs, while biosynthesis of amino acids and the Notch signaling pathway were among the down-regulated DEGs. Showing GO enrichment were cardiac muscle cell–cardiac muscle cell adhesion and microvillus membrane for up-regulated DEGs and negative regulation of osteoblast differentiation and dendrites for down-regulated DEGs. Subsequently, myosin VB (MYO5B), discs, large homolog 2(DLG2), axin 2 (AXIN2), protein tyrosine kinase 7 (PTK7), Notch homolog 1 (NOTCH1), androgen receptor (AR), cyclin D1 (CCND1) and Rho family GTPase 3 (RND3) were diagnosed as the top hub genes in the up- and down-regulated PPI network and modules. In addition, GATA binding protein 6 (GATA6), ectonucleotide pyrophosphatase/phosphodiesterase 5 (ENPP5), cyclin D1 (CCND1) and tubulin, beta 2A (TUBB2A) were diagnosed as the top hub genes in the up- and down-regulated target gene–miRNA network, while tubulin, beta 2A (TUBB2A), olfactomedin-like 1 (OLFML1), prostate adrogen-regulated mucin-like protein 1 (PARM1) and aldehyde dehydrogenase 4 family, member A1 (ALDH4A1)were diagnosed as the top hub genes in the up- and down-regulated target gene–TF network. The current study based on the GEO database provides a novel understanding regarding the mechanism of insulin resistance and may provide novel therapeutic targets.
Highlights
The current study based on the Gene Expression Omnibus (GEO) database provides a novel understanding regarding the mechanism of insulin resistance and may provide novel therapeutic targets
Obesity is a major risk factor for non-insulin-dependent diabetes mellitus (NIDDM), which has a prevalence that is positively correlated with body mass index [1]
Modified fatty acid metabolism contributes to insulin resistance in patients with non-insulin-dependent diabetes mellitus [6]
Summary
Obesity is a major risk factor for non-insulin-dependent diabetes mellitus (NIDDM), which has a prevalence that is positively correlated with body mass index [1]. Biomolecules 2019, 9, 37 complicated metabolic disorder which arises from a complex interaction of a vast number of genetic and environmental factors [2]. High plasma free fatty acid concentrations are typically linked with many insulin-resistant states, including obesity and NIDDM [5]. Modified fatty acid metabolism contributes to insulin resistance in patients with non-insulin-dependent diabetes mellitus [6]. High secretion of tumor necrosis factor-alpha (TNF-α) [7], interleukin-6 (IL-6) [8], monocyte chemoattractant protein-1 (MCP-1) [9], and additional products of macrophages [10] by adipose tissue with low sensitivity to insulin has been detected in obesity
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
