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In individuals with T2DM, the infiltration of macrophages into pancreatic islets results in islet inflammation that impairs beta cell function, as evidenced by increased apoptosis and decreased glucose\u2010stimulated insulin secretion. The present study aimed to investigate the effects of non\u2010lethal sonodynamic therapy (NL\u2010SDT) on bone marrow\u2010derived macrophages (BMDMs) exposed to high glucose and palmitic acid (HG\/PA). These findings indicate that NL\u2010SDT facilitates the expression of DRP1 through the transient production of mitochondrial ROS, which subsequently promotes mitophagy. This mitophagy was shown to limit the activation of the NLRP3 inflammasome and the secretion of IL\u20101\u03b2 in BMDMs exposed to HG\/PA. In co\u2010culture experiments, beta cells exhibited significant dysfunction when interacting with HG\/PA\u2010treated BMDMs. However, this dysfunction was markedly alleviated when the BMDMs had undergone NL\u2010SDT treatment. Moreover, NL\u2010SDT was found to lower blood glucose levels and elevate serum insulin concentrations in db\/db mice. Furthermore, NL\u2010SDT effectively reduced the infiltration of F4\/80\u2010positive macrophages and the expression of CASP1 within islets. These findings provide fundamental insights into the mechanisms through which NL\u2010SDT may serve as a promising approach for the treatment of T2DM.<\/jats:p>","DOI":"10.1096\/fj.202402008r","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T11:24:41Z","timestamp":1731929081000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Non\u2010lethal sonodynamic therapy inhibits high glucose and palmitate\u2010induced macrophage inflammasome activation through\n                    <scp>mtROS<\/scp>\n                    \u2010\n                    <scp>DRP1<\/scp>\n                    \u2010mitophagy pathway"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3346-8754","authenticated-orcid":false,"given":"Jiayu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathophysiology Harbin Medical University  Harbin P. R. 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