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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Public Health of Jilin University, Changchun, China; Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; Ruian Center of Chinese-American Research Institute for Diabetic Complications, the Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, China.
authors.forename: Minglong
authors.initials: M
authors.lastname: Shao
authors.affiliation: Ruian Center of Chinese-American Research Institute for Diabetic Complications, the Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, China.
authors.forename: Xuemian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; School of Pharmacy, Wenzhou Medical College, Wenzhou, China.
authors.forename: Weitao
authors.initials: W
authors.lastname: Cong
authors.affiliation: School of Public Health of Jilin University, Changchun, China; Changchun Institute for Food and Drug Control, Changchun, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xing
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, the First Hospital of Jilin University, Changchun, China.
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; School of Pharmacy, Wenzhou Medical College, Wenzhou, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; School of Pharmacy, Wenzhou Medical College, Wenzhou, China.
authors.forename: Litai
authors.initials: L
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Wenzhou Medical College, Wenzhou, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Public Health of Jilin University, Changchun, China.
authors.forename: Juancong
authors.initials: J
authors.lastname: Dong
authors.affiliation: School of Public Health of Jilin University, Changchun, China.
authors.forename: Shunzi
authors.initials: S
authors.lastname: Jin
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; Ruian Center of Chinese-American Research Institute for Diabetic Complications, the Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; Kosair Children's Hospital Research Institute at the Department of Pediatrics, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D006984:Hypertrophy; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008297:Male; D055432:Metabolomics; D051379:Mice; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011827:Radiation; D011829:Radiation Dosage; D014916:Whole-Body Irradiation; D014965:X-Rays
chemical_list: D051057:Proto-Oncogene Proteins c-akt