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Exosomes of adipose-derived mesenchymal stem cells loaded with globular adiponectin improve islet function for type 2 diabetes
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DOI：10.4252/wjsc.v18.i3.115363.png)
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Abstract
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BACKGROUND 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. AIM To develop a new synergistic therapeutic strategy based on adipose-derived mesenchymal stem cells Exos loaded with gAd (gAd-Exo). METHODS 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. RESULTS gAd-Exo treatment significantly ameliorated hyperglycemia, improved pancreatic islet morphology, and reduced beta-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. CONCLUSION 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 beta 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.
Keywords:
Adipose-derived mesenchymal stem cells
Exosomes
Type 2 diabetes mellitus
Insulin sensitivity
Islet function
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