Exploring the therapeutic potential of Rutin and Morin in Type 2 Diabetes: A transcriptomics and molecular dynamics simulation for proteins

Type 2 diabetes (T2D) is a chronic, multifactorial disorder characterized by hyperglycemia or hyporinsulinemia. Despite numerous previous studies, its prevalence and associated complications continue to pose a significant global health concern. This study primarily focuses on identifying and investigating potential biomarkers and underlying molecular mechanisms that substantially impact T2D progression. A human microarray dataset (GSE20966 & GSE41762) exclusively containing pancreatic beta cells was sourced from the GEO database to facilitate the following research. The analysis of differentially expressed genes (DEGs) and the construction of co-expression networks were carried out using R and Bioconductor packages. The differentially co-expressed genes were further utilized to analyse hub genes and comprehensively characterize their functional importance by STRING, DAVID and ClueGo. The analysis conducted in this study emphasises the significance of seven hub genes (CEL, CPA1, CPB1, CTRB2, CEL3B, PLA2G1B, and REG1A) primarily implicated in T2D-associated molecular pathways such as pancreatic secretion, protein digestion and absorption and fat digestion and absorption. Among seven hub markers, direct scientific evidence underscores the role of PLA2G1B as a causative factor in the development of T2D. Therefore, further MD simulation for proteins study was conducted to comprehend the possible inhibition of the gene thereby reducing the severity of T2D. The study includes molecular docking and MD Simulation where it was established that phytocompounds (Rutin and Morin) for an instant posses higher binding affinity towards PLA2G1B in comparison to the standard inhibitors n-(p-Amylcinnamoyl) anthranilic acid. Thus, overall, it can be predicted that the flavonoids RU and MO could target PLA2G1B and might serve as a focused therapeutic approach for treating patients with T2D.