The Effects Of Astaxanthin Silica Redox Nanoparticles On Insulin Resistance And Adipogenic Differentiation In Adipose Tissue-Derived Mesenchymal Stem Cells Under High Glucose Concentrations

Abstract

Type 2 diabetes (T2DM) specifically entails insulin resistance, where the body exhibits reduced responsiveness to insulin. In this project, (adipose tissue-derived mesenchymal stem cells) AT-MSCs were utilized to establish a disease model mimicking insulin resistance under high D-glucose conditions. Notably, excessive reactive oxygen species (ROS) production is implicated in insulin resistance among T2DM patients and serves as a catalyst for adipogenic differentiation. Exposure to elevated D-glucose concentrations amplifies ROS generation and elevates the expression of insulin resistance-related genes including EGR-1, PTEN, and GGPS-1, potentially exacerbating insulin resistance in ATMSCs and augmenting adipocyte differentiation. This research will focus on incorporating astaxanthin into silica redox nanoparticles (asta@siRNP), aiming to notably increase its bioavailability. Additionally, the antioxidant capacity is anticipated to be further enhanced by combining astaxanthin with Peg-b-P(MNT-r-si-st), a polymer recognized for its excellent antioxidant properties.Asta@siRNP has demonstrated the capacity to mitigate ROS by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay, prompting exploration into insulin resistance research amidst high glucose environments. Although a segment of the experiment suggested potential of asta@siRNP in reducing insulin resistance, particularly notable with favorable outcomes for the EGR-1 gene across all concentrations and especially at the highest concentration (10 µg/mL) concerning the GGPS-1 gene, definitive conclusions are yet to be drawn. To accurately assess asta@siRNP's efficacy in reducing insulin resistance, future projects should incorporate evaluation experiments specifically targeting insulin resistance. Additionally, ROS generation emerges not merely as a byproduct of differentiation but as an active driver of adipocyte differentiation. Remarkably, Oil Red O staining revealed that under high D-glucose conditions promoting increased differentiation, lipid droplet formation gradually decreased with increasing asta@siRNP concentration, underscoring its potential in mitigating the adverse effects of D-glucose on adipocyte differentiation. These findings highlight asta@siRNP promise for comprehensive exploration in attenuating the effects of diabetes in future research endeavors.