Carter Calvin S, Huang Sunny C, Searby Charles C, Cassaidy Benjamin, Miller Michael J, Grzesik Wojciech J, Piorczynski Ted B, Pak Thomas K, Walsh Susan A, Acevedo Michael, Zhang Qihong, Mapuskar Kranti A, Milne Ginger L, Hinton Antentor O, Guo Deng-Fu, Weiss Robert, Bradberry Kyle, Taylor Eric B, Rauckhorst Adam J, Dick David W, Akurathi Vamsidhar, Falls-Hubert Kelly C, Wagner Brett A, Carter Walter A, Wang Kai, Norris Andrew W, Rahmouni Kamal, Buettner Garry R, Hansen Jason M, Spitz Douglas R, Abel E Dale, Sheffield Val C
Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA.
Department of Pediatrics and Division of Medical Genetics and Genomics, University of Iowa Hospitals & Clinics, Iowa City, IA, USA; Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Cell Metab. 2020 Oct 6;32(4):561-574.e7. doi: 10.1016/j.cmet.2020.09.012.
Aberrant redox signaling underlies the pathophysiology of many chronic metabolic diseases, including type 2 diabetes (T2D). Methodologies aimed at rebalancing systemic redox homeostasis have had limited success. A noninvasive, sustained approach would enable the long-term control of redox signaling for the treatment of T2D. We report that static magnetic and electric fields (sBE) noninvasively modulate the systemic GSH-to-GSSG redox couple to promote a healthier systemic redox environment that is reducing. Strikingly, when applied to mouse models of T2D, sBE rapidly ameliorates insulin resistance and glucose intolerance in as few as 3 days with no observed adverse effects. Scavenging paramagnetic byproducts of oxygen metabolism with SOD2 in hepatic mitochondria fully abolishes these insulin sensitizing effects, demonstrating that mitochondrial superoxide mediates induction of these therapeutic changes. Our findings introduce a remarkable redox-modulating phenomenon that exploits endogenous electromagneto-receptive mechanisms for the noninvasive treatment of T2D, and potentially other redox-related diseases.
异常的氧化还原信号传导是包括2型糖尿病（T2D）在内的许多慢性代谢性疾病病理生理学的基础。旨在重新平衡全身氧化还原稳态的方法取得的成功有限。一种非侵入性、持续性的方法将能够长期控制氧化还原信号传导以治疗T2D。我们报告，静磁场和电场（sBE）可非侵入性地调节全身谷胱甘肽（GSH）与氧化型谷胱甘肽（GSSG）的氧化还原对，以促进更健康的、具有还原性的全身氧化还原环境。引人注目的是，当应用于T2D小鼠模型时，sBE在短短3天内就能迅速改善胰岛素抵抗和葡萄糖不耐受，且未观察到不良反应。用超氧化物歧化酶2（SOD2）清除肝线粒体中氧代谢的顺磁性副产物可完全消除这些胰岛素增敏作用，表明线粒体超氧化物介导了这些治疗性变化的诱导。我们的研究结果引入了一种显著的氧化还原调节现象，该现象利用内源性电磁感受机制对T2D以及潜在的其他氧化还原相关疾病进行非侵入性治疗。
