Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.
<h4>Background</h4>Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resi...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0092574 |
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| author | Minglong Shao Xuemian Lu Weitao Cong Xiao Xing Yi Tan Yunqian Li Xiaokun Li Litai Jin Xiaojie Wang Juancong Dong Shunzi Jin Chi Zhang Lu Cai |
| author_facet | Minglong Shao Xuemian Lu Weitao Cong Xiao Xing Yi Tan Yunqian Li Xiaokun Li Litai Jin Xiaojie Wang Juancong Dong Shunzi Jin Chi Zhang Lu Cai |
| author_sort | Minglong Shao |
| collection | DOAJ |
| description | <h4>Background</h4>Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.<h4>Objective</h4>The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.<h4>Methods</h4>Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.<h4>Results</h4>HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.<h4>Conclusion</h4>These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress. |
| format | Article |
| id | doaj-art-4cfe34829ece47cbb833dd6b77250179 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-4cfe34829ece47cbb833dd6b772501792025-08-20T02:36:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9257410.1371/journal.pone.0092574Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.Minglong ShaoXuemian LuWeitao CongXiao XingYi TanYunqian LiXiaokun LiLitai JinXiaojie WangJuancong DongShunzi JinChi ZhangLu Cai<h4>Background</h4>Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.<h4>Objective</h4>The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.<h4>Methods</h4>Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.<h4>Results</h4>HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.<h4>Conclusion</h4>These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.https://doi.org/10.1371/journal.pone.0092574 |
| spellingShingle | Minglong Shao Xuemian Lu Weitao Cong Xiao Xing Yi Tan Yunqian Li Xiaokun Li Litai Jin Xiaojie Wang Juancong Dong Shunzi Jin Chi Zhang Lu Cai Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. PLoS ONE |
| title | Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. |
| title_full | Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. |
| title_fullStr | Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. |
| title_full_unstemmed | Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. |
| title_short | Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. |
| title_sort | multiple low dose radiation prevents type 2 diabetes induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress |
| url | https://doi.org/10.1371/journal.pone.0092574 |
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