Integrating transcriptomics and proteomics to understand the molecular mechanisms underlying the pathogenesis of type 2 diabetes mellitus

Abstract

The liver plays an important role in glucose regulation, and their dysfunction is closely associated with the development of type 2 diabetes mellitus (T2DM), and insulin resistance (IR) in hepatocyte mediate the pathogenesis of diabetes mellitus. In T2DM rats and their correlated control, we investigated various genes expression at transcriptional and translational level by utilizing transcriptomic using RNA sequencing (RNA-seq) and proteomics using isobaric tags for relative and absolute quantification (iTRAQ) to disclose potential candidates for Type 2 diabetes diagnosis and therapy. We found the lecithin retinol acyltransferase (Lrat) gene regulate hepatocyte IR in T2DM. Furthermore, BRL-3A cells, rat liver cells, worked as the IR model in vitro study. Hence, Lrat gene was overexpressed in BRL-3A cells to explore the role of Lrat gene in IR by measuring the cellular glucose consumption, TCHO, and LDL-C levels. Finally, we found that Lrat gene can improve the level of glycolipid metabolism in BRL-3A cells and reduce the degree of IR in BRL-3A cells. Therefore, further exploration of Lrat gene related molecular mechanism is meaningful.