Introduction
Metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity are major public health issues worldwide. Exosomes contribute to the pathophysiology of these diseases by mediating intercellular communication among adipose tissue, liver, pancreas, and muscle cells.
Exosomes and Insulin Resistance
- Adipocyte-derived exosomes carry miRNAs (e.g., miR-27a, miR-34a) that modulate insulin signaling pathways in muscle and liver cells, promoting insulin resistance [1].
- Liver-derived exosomes influence systemic glucose homeostasis by transferring bioactive lipids and proteins [2].
Exosomes in Diabetes Mellitus
- Circulating exosomal miRNAs serve as early biomarkers of pancreatic beta-cell dysfunction and insulin resistance [3].
- Exosomes from diabetic patients show altered cargo profiles, including inflammatory cytokines and microRNAs contributing to vascular complications [4].
Role in Obesity
- Exosomes mediate crosstalk between adipose tissue and immune cells, driving chronic inflammation and metabolic dysregulation [5].
- Obesity-associated exosomes can impair endothelial function, promoting cardiovascular risk.
Therapeutic Applications
- MSC-derived exosomes improve insulin sensitivity and reduce inflammation in diabetic animal models [6].
- Exosome-mediated delivery of siRNAs targeting key metabolic genes offers a novel intervention strategy.
- Lifestyle interventions may alter exosome profiles, serving as markers of therapeutic efficacy.
Challenges and Future Directions
- Need for standard biomarkers in metabolic exosomes.
- Understanding tissue-specific exosome effects.
- Scaling exosome-based therapies for clinical use.
Conclusion
Exosomes are central mediators and potential therapeutic targets in metabolic disorders. Advances in this field promise improved diagnosis and personalized treatment approaches.
📚 References
- Ying W, et al. Adipose tissue macrophage-derived exosomal miRNAs modulate insulin sensitivity in mice. Science. 2017;355(6321):556-560. https://doi.org/10.1126/science.aai8521
- Hirsova P, et al. Hepatocyte-derived extracellular vesicles promote liver inflammation and fibrosis via macrophage activation. J Hepatol. 2016;65(5):1002-1012. https://doi.org/10.1016/j.jhep.2016.06.026
- Zampetaki A, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107(6):810-817. https://doi.org/10.1161/CIRCRESAHA.109.215827
- Freeman DW, et al. Altered extracellular vesicle concentration, cargo, and function in type 2 diabetes mellitus. Diabetes. 2018;67(11):2377-2388. https://doi.org/10.2337/db18-0316
- Deng ZB, et al. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes. 2009;58(11):2498-2505. https://doi.org/10.2337/db09-0227
- Zhu M, et al. Mesenchymal stem cell-derived exosomes ameliorate insulin resistance in type 2 diabetes. Front Pharmacol. 2020;11:1221. https://doi.org/10.3389/fphar.2020.01221