Ying Song1, Wei Ding2, Yun Bei3, Yan Xiao4, Hai-Da Tong5, Li-Bo Wang6, Li-Yao Ai6. 1. Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China. Electronic address: songying@zjut.edu.cn. 2. Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China; VivaChek Biotech (Hangzhou) Co., Ltd., 2nd Floor, Building No. 2, 146 East Chaofeng Road, Yuhang Economic Development Zone, Hangzhou, Zhejiang, 311100, PR China. Electronic address: 1601868721@qq.com. 3. Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China. Electronic address: 1250573211@qq.com. 4. Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China; St. Jude Medical (Shang Hai) Co., Ltd., Unit 02-07, 15th Floor, 688 West Nanjing Road, Jingan Distrist, Shanghai, 200041, PR China. Electronic address: wodehaha2008@126.com. 5. Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China. Electronic address: 158630342@qq.com. 6. Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China.
Abstract
PURPOSE: To investigate the neuroprotective effects of insulin on diabetic encephalopathy and its mechanism. EXPERIMENTAL AND APPROACH: The diabetic model was established by injection of streptozotocin. Behavior examinations were conducted by the Morris water maze. Histopathological alterations were detected by HE staining. ROS, CAT levels and SOD activity were measured using a microplate reader. In vitro, the viability of wild type and knock-down PC12 cells was detected by MTT assay, the morphology of cells was monitored under a microscope. The subcellular distribution of Nrf2 was observed by western blotting and immunohistochemistry. KEY RESULTS: Evident oxidative stress injury was observed in diabetic rats and H2O2-induced PC12 cells. Insulin not only protect diabetic rat from oxidative stress injury but also significantly inhibited H2O2-induced apoptosis and intracellular ROS in cells. In addition, the level of malondialdehyde was reduced, and the activities of superoxide dismutase, catalase and glutathione peroxidase were augmented in both diabetic rats and PC12 cells. Interestingly, insulin promoted the translocation of Nrf2 into the nucleus and activation of downstream antioxidant protein expression. Further, the Nrf2 knockdown cells suffered more serious H2O2-induced damage than the wild PC12 cells. Moreover, insulin had no significant protective effect on knockdown cells with H2O2-damage. CONCLUSION AND IMPLICATIONS: Collectively, our results suggested that insulin significantly inhibited neuronal damage through the Nrf2 signaling pathway, which regulates endogenous oxidant-antioxidant balance, therefore, insulin may be a potential protective agent for the treatment of oxidative stress-induced diabetic encephalopathy.
PURPOSE: To investigate the neuroprotective effects of insulin on diabetic encephalopathy and its mechanism. EXPERIMENTAL AND APPROACH: The diabetic model was established by injection of streptozotocin. Behavior examinations were conducted by the Morris water maze. Histopathological alterations were detected by HE staining. ROS, CAT levels and SOD activity were measured using a microplate reader. In vitro, the viability of wild type and knock-down PC12 cells was detected by MTT assay, the morphology of cells was monitored under a microscope. The subcellular distribution of Nrf2 was observed by western blotting and immunohistochemistry. KEY RESULTS: Evident oxidative stress injury was observed in diabeticrats and H2O2-induced PC12 cells. Insulin not only protect diabeticrat from oxidative stress injury but also significantly inhibited H2O2-induced apoptosis and intracellular ROS in cells. In addition, the level of malondialdehyde was reduced, and the activities of superoxide dismutase, catalase and glutathione peroxidase were augmented in both diabeticrats and PC12 cells. Interestingly, insulin promoted the translocation of Nrf2 into the nucleus and activation of downstream antioxidant protein expression. Further, the Nrf2 knockdown cells suffered more serious H2O2-induced damage than the wild PC12 cells. Moreover, insulin had no significant protective effect on knockdown cells with H2O2-damage. CONCLUSION AND IMPLICATIONS: Collectively, our results suggested that insulin significantly inhibited neuronal damage through the Nrf2 signaling pathway, which regulates endogenous oxidant-antioxidant balance, therefore, insulin may be a potential protective agent for the treatment of oxidative stress-induced diabetic encephalopathy.
Authors: Adrián Jordá; Martin Aldasoro; Ignacio Campo-Palacio; Jose M Vila; Constanza Aldasoro; Juan Campos-Campos; Carlos Colmena; Sandeep Kumar Singh; Elena Obrdor; Soraya L Valles Journal: Int J Mol Sci Date: 2022-10-09 Impact factor: 6.208