<em>In&nbsp;silico</em> prediction and validation of potential therapeutic genes in pancreatic &beta;‑cells associated with type 2 diabetes

Abstract

Diabetes mellitus is becoming a major health burden worldwide. Pancreatic β-cell death is a characteristic of type 2 diabetes (T2D), but the underlying mechanisms of pancreatic β-cell death remain unknown. Therefore, the aim of the present study was to identify potential targets in the pancreatic islet of T2D. The GSE20966 dataset was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by using the GEO2R tool. The Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analysis of DEGs were further assessed using the Database for Annotation, Visualization and Integrated Discovery. Furthermore, protein-protein interaction (PPI) networks were constructed for the up-and downregulated genes using STRING databases and were then visualized with Cytoscape. The body weight, fasting blood glucose (FBG), pancreatic index and biochemistry parameters were measured in db/db mice. Moreover, the morphology of the pancreas was detected by hematoxylin and eosin staining, and hub genes were assessed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. In total, 570 DEGs were screened, including 376 upregulated and 194 downregulated genes, which were associated with 'complement activation, classical pathway', 'proteolysis', 'complement activation' and 'pancreatic secretion pathway'. It was found that the body weight, FBG, alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, blood urea nitrogen, creatinine, fasting serum insulin, glucagon and low-density lipoprotein cholesterol levels were significantly higher in db/db mice, while high-density lipoprotein cholesterol levels and the pancreatic index were significantly decreased. Furthermore, albumin, interleukin-8, CD44, CC motif chemokine ligand 2, hepatocyte growth factor, cystic fibrosis transmembrane conductance regulator, histone cluster 1 H2B family member n, mitogen-activated protein kinase 11 and neurotrophic receptor tyrosine kinase 2 were identified as hub genes in PPI network. RT-qPCR and western blotting results demonstrated the same expression trend in hub genes as found by the bioinformatics analysis. Therefore, the present study identified a series of hub genes involved in the progression of pancreatic β-cell, which may help to develop effective therapeutic strategy for T2D.

Association of MicroRNA-146a with Type 1 and 2 Diabetes and their Related Complications

“…Diabetes is responsible for 6.8 percent of worldwide mortality in the 20-79 age range and is a primary reason for decreased life expectancy [5,6]. About 10% of diabetic patients have type 1 diabetes (T1D), which is char-acterized by an uncontrolled and destructive immune response to pancreatic beta cells [7,8], whereas the remaining DM patients have type 2 diabetes (T2D), whose main risk factors include overweight, insufficient physical activity, and smoking [9,10]. Numerous clinical studies have shown that lifestyle modifications may successfully prevent the progression of T2D.…”

Crosstalk Communications Between Islets Cells and Insulin Target Tissue: The Hidden Face of Iceberg

“…The treatment of b-cells by HGF increases the phosphorylation of IRS2, AKT and ERK (138). This increase is the response of MET activation by HGF, which induce the formation of a MET-Insulin receptor complex responsible of an increase in insulin signal (136,138,139).…”