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

• Published in: PloS one 2014-03, Vol.9 (3), p.e92574
• Main Authors: Shao, Minglong, Lu, Xuemian, Cong, Weitao, Xing, Xiao, Tan, Yi, Li, Yunqian, Li, Xiaokun, Jin, Litai, Wang, Xiaojie, Dong, Juancong, Jin, Shunzi, Zhang, Chi, Cai, Lu
• Format: Article
• Language: English
• Subjects: AKT protein; Analysis; Animals; Apoptosis; Attenuation; Biology and Life Sciences; Blood glucose; Calories; Damage prevention; Diabetes mellitus; Diabetic Nephropathies - etiology; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; Diet, High-Fat; Disease Models, Animal; Dyslipidemia; Dyslipidemias - etiology; Dyslipidemias - metabolism; Dyslipidemias - prevention & control; Exposure; Fibrosis; Glucose; High fat diet; Hypertrophy; Inflammation; Inflammation - metabolism; Injury prevention; Insulin; Insulin Resistance; Ionizing radiation; Kidney - pathology; Kidney - physiopathology; Kidneys; Male; Medicine and Health Sciences; Metabolic disorders; Metabolomics; Mice; Obesity; Oxidation resistance; Oxidative Stress; Physical Sciences; Physiological aspects; Proto-Oncogene Proteins c-akt - metabolism; Radiation; Radiation damage; Radiation Dosage; Renal function; Rodents; Streptozocin; Type 2 diabetes; Whole-Body Irradiation; X-Rays
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092574

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. The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. 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. 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. 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.