Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model.

Abstract

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

• Authors: Minglong Shao, Lechu Yu, Fangfang Zhang, Xuemian Lu, Xiaokun Li, Peng Cheng, Xiufei Lin, Luqing He, Shunzi Jin, Yi Tan, Hong Yang, Chi Zhang, Lu Cai
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 309 Issue 1 Pg. E45-54 (Jul 01 2015) ISSN: 1522-1555 [Electronic] United States
• PMID: 25968574 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Radiation-Sensitizing Agents
• fibroblast growth factor 21
• Streptozocin
• Fibroblast Growth Factors

Topics

• Animals
• Diabetes Mellitus, Experimental (complications, drug therapy, radiotherapy)
• Diabetes Mellitus, Type 2 (complications, drug therapy, radiotherapy)
• Diabetic Nephropathies (prevention & control)
• Fibroblast Growth Factors (therapeutic use)
• Kidney (drug effects, radiation effects)
• Male
• Mice
• Mice, Inbred C57BL
• Radiation Dosage
• Radiation-Sensitizing Agents (therapeutic use)
• Streptozocin
• Whole-Body Irradiation (methods)
• X-Rays