MicroRNAs Dependent G‐ELNs Based Intervention Improves Glucose and Fatty Acid Metabolism While Protecting Pancreatic β‐Cells in Type 2 Diabetic Mice

Abstract Metabolic disorders such as Type 2 diabetes mellitus (T2DM) imposes a significant global health burden. Plant‐derived exosome like nanoparticles (P‐ELNs) have emerged as a promising therapeutic alternate for various diseases. Present data demonstrates that treatment with Ginger‐derived exosome like nanoparticles (G‐ELNs) enhance insulin dependent glucose uptake, downregulate gluconeogenesis and oxidative stress in insulin resistant HepG2 cells. Furthermore, oral administration of G‐ELNs in T2DM mice decreases fasting blood glucose levels and improves glucose tolerance as effectively as metformin. These improvements are attributed to the enhanced phosphorylation of Protein kinase B (Akt‐2), the phosphatidylinositol 3‐kinase at serine 474 which consequently leads to increase in hepatic insulin sensitivity, improvement in glucose homeostasis and decrease in ectopic fat deposition. Oral administration of G‐ELNs also exerts protective effect on Streptozotocin (STZ)‐induced pancreatic β‐cells damage, contributing to systemic amelioration of T2DM. Further, as per computational tools, miRNAs present in G‐ELNs modulate the phosphatidylinositol 3‐kinase (PI3K)/Akt‐2 pathway and exhibit strong interactions with various target mRNAs responsible for hepatic gluconeogenesis, ectopic fat deposition and oxidative stress. Furthermore, synthetic mimic of G‐ELNs miRNA effectively downregulates its target mRNA in insulin resistant HepG2 cells. Overall, the results indicate that the miRNAs present in G‐ELNs target hepatic metabolism thus, exerting therapeutic effects in T2DM.