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Assessment of early renal damage in diabetic rhesus monkeys

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Abstract

The objectives of the study were to improve the model system of diabetic nephropathy in nonhuman primates and assess the early renal damage. Diabetes was induced in monkeys by streptozotocin, and the animals were administered exogenous insulin to control blood glucose (BG). Animals were divided into four groups, including the normal group (N = 3), group A (streptozotocin diabetic model with control of BG < 10 mmol/L, N = 3), group B (streptozotocin diabetic model with control of BG between 15 and 20 mmol/L, N = 4), and group C (streptozotocin diabetic model with control of BG between 15 and 20 mmol/L and high-sodium and high-fat diet, N = 4). The following parameters were evaluated: (1) blood biochemistry and routine urinalysis, (2) color Doppler ultrasound, (3) angiography, (4) renal biopsy, and (5) renal fibrosis-related gene expression levels. Animals in group C developed progressive histologic changes with typical diabetic nephropathy resembling diabetic nephropathy in human patients and exhibited accelerated development of diabetic nephropathy compared with other nonhuman primate models. Significant changes in the expression of the Smad2/3 gene and eNOS in renal tissue were also observed in the early stage of diabetic nephropathy. In conclusion, our model is an excellent model of diabetic nephropathy for understanding the pathogenesis of diabetic nephropathy.

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Acknowledgments

This study was supported by the Program of Natural Science Foundation of China (No. 81370824) and National Program for High Technology Research and Development of China (No. 2012AA020702).

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Authors and Affiliations

  1. Key Lab of Transplant Engineering and Immunology, Ministry of Health; Regenerative Medicine Research Center, West China Hospital, Sichuan University, No.1 Keyuan 4th Road, Gao Peng Ave, Chengdu, 610041, Sichuan, People’s Republic of China

    Dan Wang, Jingping Liu, Sirong He, Chengshi Wang, Younan Chen, Guang Yang, Guangneng Liao, Lan Li, Meimei Shi, Yujia Yuan, Jiuming Zhao, Jingqiu Cheng & Yanrong Lu

  2. Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Lichaun Yang & Fang Liu

  3. Department of Endocrine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Yan Ren & Haoming Tian

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  1. Dan Wang
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Corresponding authors

Correspondence to Jingqiu Cheng or Yanrong Lu.

Electronic supplementary material

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Supplementary material 1 (DOC 17 kb)

12020_2014_211_MOESM2_ESM.doc

Supplementary Figure 1. Renal ultrasound blood flow distribution and spectrum in control and experimental groups(DOC 769 kb)

12020_2014_211_MOESM3_ESM.doc

Supplementary Figure 2. Retinal capillaries was normal in fundus examination. Left and right eyes of monkey from group C (DOC 766 kb)

12020_2014_211_MOESM4_ESM.doc

Supplementary Figure 3. Representative mages of H&E stained kidneys from control and 3 experimental groups before we imposed any interventions. Scale bar 100 μm (DOC 1815 kb)

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Wang, D., Liu, J., He, S. et al. Assessment of early renal damage in diabetic rhesus monkeys. Endocrine 47, 783–792 (2014). https://doi.org/10.1007/s12020-014-0211-4

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  • DOI: https://doi.org/10.1007/s12020-014-0211-4

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