Published online Mar 26, 2026. doi: 10.4252/wjsc.v18.i3.115363
Revised: November 23, 2025
Accepted: January 26, 2026
Published online: March 26, 2026
Processing time: 161 Days and 4.5 Hours
The global prevalence of type 2 diabetes mellitus (T2DM) is increasing. Although globular adiponectin (gAd) shows potential in improving islet function, its clinical application is limited by rapid clearance. Given the promising prospects of adipose-derived mesenchymal stem cell exosomes (Exos) in targeted therapy, whether this nanocarrier can enhance gAd’s efficacy in improving islet function warrants significant research attention.
To develop a new synergistic therapeutic strategy based on adipose-derived mesenchymal stem cells Exos loaded with gAd (gAd-Exo).
A T2DM rat model was established using a high-fat diet and streptozotocin. Rats were randomized into control, T2DM, T2DM + gAd, T2DM + Exo, and T2DM + gAd-Exo groups, receiving respective treatments via tail vein injection for four weeks. Pancreatic tissues were subjected to histological, immunohistochemical, and biochemical analyses. Meanwhile in vitro experiments assessed the protective effects of gAd-Exo on palmitic acid-injured INS-1 cells.
gAd-Exo treatment significantly ameliorated hyperglycemia, improved pancreatic islet morphology, and reduced β-cell apoptosis compared to other groups. It enhanced insulin sensitivity and down-regulated glucagon expression. Mechanistically, gAd-Exo activated the AMP-activated protein kinase/acetyl-CoA carboxylase signaling pathway. In vitro, gAd-Exo superiorly mitigated palmitic acid-induced oxidative stress and apoptosis in INS-1 cells.
This study shows that the combination of gAd and Exo produced a significant synergistic effect. gAd-Exo can relieve type 2 diabetes by reducing blood glucose, improving hyperinsulinaemia and islet function, and at the same time reducing islet β cells apoptosis. It may be achieved by activating the AMP-activated protein kinase/acetyl-CoA carboxylase pathway. The discovery provides a new strategy with synergistic regenerative potential for diabetes treatment.
Core Tip: Researchers have developed a promising new approach to treat type 2 diabetes using exosomes (Exos) derived from adipose-derived mesenchymal stem cells loaded with globular adiponectin (gAd) - referred to as gAd-Exo. The combination of gAd and Exo produced a significant synergistic effect. In a diabetic rat model, gAd-Exo significantly lowered blood glucose, reduced pancreatic islet cell death, and improved insulin sensitivity. It also helped restore the structure and function of pancreatic islets. Mechanistically, gAd-Exo activated key metabolic pathway - AMP-activated protein kinase/acetyl-CoA carboxylase - which are crucial for energy metabolism and cell survival. This study highlights the potential of Exo-mediated delivery to enhance the efficacy of therapeutic molecules like gAd, offering a targeted and sustained treatment strategy for type 2 diabetes.