Insulin is a potential antioxidant for diabetes-associated cognitive decline via regulating Nrf2 dependent antioxidant enzymes - 11/06/18
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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.
Le texte complet de cet article est disponible en PDF.Abbreviations : ARE, CAT, DMEM, DMSO, DCFH-DA, FBS, GSH-Px, H2O2, IP-3-K/PKB, Keap 1, KD, Nrf2, MDA, MTP, MTT, NADPH, NC, PC12 cell, Rh123, ROS, SOD, STZ
Keywords : Insulin, Oxidative stress, Diabetic encephalopathy, Antoxidant, Rat pheochromocytoma, NF-E2-related factor 2
Plan
☆ | This work was supported by Grants-in-aid from the Zhejiang Provincial Natural Science Foundation of China (No. LY17H090018) and the National Special Foundation for Clinical Medicine Research (No. L2011079). |
Vol 104
P. 474-484 - août 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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