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

doi:10.1371/journal.pone.0092574

科研成果详情

题名	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
作者	Shao, Minglong1,2,3; Lu, Xuemian3; Cong, Weitao2,4; Xing, Xiao 1,5; Tan, Yi2,6; Li, Yunqian 7; Li, Xiaokun2,4; Jin, Litai2,4; Wang, Xiaojie 4; Dong, Juancong 1; Jin, Shunzi 1; Zhang, Chi 2,3; Cai, Lu2,6
发表日期	2014-03-20
发表期刊	PLOS ONE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	INDUCED DNA-DAMAGE ; BREAST-CANCER PATIENTS ; APOPTOTIC CELL-DEATH ; AKT ACTIVATION ; KIDNEY-DISEASE ; POTENTIAL ROLE ; NEPHROPATHY ; OBESITY ; PROLIFERATION ; LIPOTOXICITY
摘要	Background: 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. Objective: The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. Methods: 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. Results: 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. Conclusion: 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.
资助项目	National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81000294, 81370917]; Wenzhou Medical University [QTJ13005]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1 R01 DK091338-01A1]; Wenzhou Medical University; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LQ12H07002, LQ13H020005]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK091338] Funding Source: NIH RePORTER
出版者	PUBLIC LIBRARY SCIENCE
出版地	SAN FRANCISCO
ISSN	1932-6203
卷号	9 期号:3 页码:e92574.
DOI	10.1371/journal.pone.0092574
页数	17
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000333352800129
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	24651118
PMC记录号	PMC3961432
SCOPUSEID	2-s2.0-84898634400
通讯作者地址	[Jin, Shunzi]Jilin Univ, Sch Publ Hlth, Changchun 130023, Peoples R China.
Scopus学科分类	Multidisciplinary
引用统计	被引频次：50[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/9801
专题	温州医科大学药学院（分析测试中心）其他_附属第三医院（瑞安市人民医院）
通讯作者	Jin, Shunzi
作者单位	1.Jilin Univ, Sch Publ Hlth, Changchun 130023, Peoples R China; 2.Wenzhou Med Univ, Chinese Amer Res Inst Diabet Complicat, Wenzhou, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 3, Chinese Amer Res Inst Diabet Complicat, Ruian Ctr, Wenzhou, Peoples R China; 4.Wenzhou Med Coll, Sch Pharm, Wenzhou, Peoples R China; 5.Changchun Inst Food & Drug Control, Changchun, Peoples R China; 6.Univ Louisville, Dept Pediat, Kosair Childrens Hosp Res Inst, Louisville, KY 40292 USA; 7.Jilin Univ, Hosp 1, Dept Neurosurg, Changchun 130023, Peoples R China
第一作者单位	温州医科大学; 其他_附属第三医院（瑞安市人民医院）
推荐引用方式 GB/T 7714	Shao, Minglong,Lu, Xuemian,Cong, Weitao,et al. 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[J]. PLOS ONE,2014,9(3):e92574..
APA	Shao, Minglong., Lu, Xuemian., Cong, Weitao., Xing, Xiao., Tan, Yi., ... & Cai, Lu. (2014). 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, 9(3), e92574..
MLA	Shao, Minglong,et al."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 9.3(2014):e92574..