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
Authors: Juancong Dong
Yi Tan
Xiao Xing
Xiaokun Li
Xiaojie Wang
Weitao Cong
Minglong Shao
Lu Cai
Shunzi Jin
Litai Jin
Yunqian Li
Chi Zhang
Xuemian Lu
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Dyslipidemia; Lipotoxicity; Insulin resistance; Inflammation; Oxidative stress
Affiliations: 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., Ruian Center of Chinese-American Research Institute for Diabetic Complications, the Third Affiliated Hospital of the Wenzhou Medical University, Wenzhou, China., Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, China; School of Pharmacy, Wenzhou Medical College, Wenzhou, China., School of Public Health of Jilin University, Changchun, China; Changchun Institute for Food and Drug Control, Changchun, China., 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., Department of Neurosurgery, the First Hospital of Jilin University, Changchun, China., School of Pharmacy, Wenzhou Medical College, Wenzhou, China., 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.

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. 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. 

Retracted: No

PubPeer comments:
 Images in Fig 6C resemble those in Fig 7C of Cell Death and Disease (2017) 8, e3037; doi:10.1038 cddis.2017.394, PMID 28880271, but some look like mirror images, and the treatments were different. ![file] , 
 Dear Dr. Mansa Singularis, Iu2019m writing to you in response to the inquiry with regard to the mentioned study with me being the corresponding author. Thank you for your interest in our work and your willingness to safeguard the integrity of scientific research. It is of great importance to me. Before seeing your inquiries, I have routinely rechecked our papers and found this problem. After carefully examining our manuscripts and raw data, we have contacted the journal and uploaded all the raw data and records to explain the problem. As long as there is a conclusion, I will immediately notify you. Thank you for your kind advice and reminding. Best regards! , 
 #2 Thank you for your reply. For your convenience, here is a link to the other paper, which seems to have additional problems: https: pubpeer.com publications 22DC7B850B2F4FABA6E3D22120F4E4 , 
 #3 #3 Many thanks for your kind reminding. Actually in our review of the paper and raw data, we have noted that in Figure 1 d the representative TRAP staining figure in the RANKL group was mistakenly selected and presented. The current figure was the RANKL+1 umol M19 group. The conclusion that M19 (1 umol) had no significant impact on osteoclastogenesis in RAW264.7 cells is not affected and the scientific integrity of the study is not compromised. We have corrected figure 1d and attached in the email to the editorial office and it is being processed now. For these studies were carried out by the same freshmen postgraduate almost simultaneously, there is a little mess in the raw data organizing. Luckily we have identified the problem, provided all the proof and it is being processed now. As long as there is a conclusion i will notify you. Many thanks again. , 
 In addition to the issues raised above, there appear to be two images in Figure 1 that overlap. *** ![file] ![file] , 
 Thank you very much for pointing out this issue. We have thoroughly checked the raw data and targeted the causes. The postgraduate mistakenly put all images in the same folder with wrongly labeled names. During combination, he probably used the wrong images taken from the same culture plate hole. To further address the problem, we are tracking the raw data, contacting the author and will inform the journal for further correction if it is true. We will keep you updated. Best regards~ , 
 #6 Thank you for your reply. Given that  all images in the same folder with wrongly labeled names how will the authors confirm that the quantification illustrated are anywhere close to correct? , 
 #7 Thank you and now we are investigating. Now we believe the problem is figure assembly. As soon as we find the problem we will inform you. Thank you again for your concern. , 
 #5 Thank you for letting us know the issue. Now we have targeted the problem that the student selected representative images by mistake. Now we are contacting the Journal for corrigendum. Best regards. ,