Life and maladies in the grey area between the up & down regulation of GATA6: Uncharted spots of beta-pancreatic islet cells.

Abstract

Abstract Death and dysfunctionality of pancreatic islet beta-cells are a centric key element in the pathogenesis of type 2 diabetes mellitus (T2DM). Saturated fatty acids are commonly circulated in diabetic and obese individuals. Elevated and chronic exposure to fatty acids has a pernicious influence on islet cells’ functionality and survival due to its capability to induce apoptosis and endoplasmic reticulum (ER) stress. However, T2DM is a heterogeneous disorder that includes genetic and environmental factors in conjunction with dyslipidaemia with a considerably high rate of morbidity and mortality. There are many genes involved in the pathogenesis that remain to be charted. Here, we show a comprehensive interrogation of GATA6 based on previously published gene expression data on the basis of stating its validity via bioinformatics analysis and reaching a new understanding. Various datasets with different patient cohorts were compared and contrasted. Gene ontology and predictive pathway analysis (e.g., Kyoto Encyclopaedia of Genes and Genomes pathway; KEGG) were used to explore interactions of numerous differentially expressed genes. Protein-protein interactions network through the STRING database has appreciated a list of key genes. GATA6 interacted with genes from pathways that were significantly enriched (FDR < 0.05) in the analysis of the KEGG pathway suggesting its close involvement, for example, 'maturity-onset diabetes of the young pathway’ and ‘pathways in cancer’. The most obvious finding to emerge from this study is that GATA6 plays an intrinsic role in islet beta cell differentiation and survival, and bioinformatics analysis allows the introduction of potentially reliable biomarkers that interact with GATA6, which required further validation studies.