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Insulin resistance acts as an independent risk factor exacerbating high-purine diet induced renal injury and knee joint gouty lesions

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Abstract

Objective and design

Insulin resistant Otsuka–Long–Evans–Tokushima Fatty (OLETF) and its control Long–Evans Tokushima Ohtsuka (LETO) rats were used to generate a model for acute hyperuricemia. Upon the onset of insulin resistance OLETF rats were feed with high-purine diet, and the development of acute hyperuricemic renal injury and gouty-like lesions was monitored. Rosiglitazone was also administered to demonstrate whether improved insulin sensitivity would prevent high-purine diet induced renal injury and gouty-like lesions.

Results

Otsuka–Long–Evans–Tokushima Fatty rats showed significant higher incidence of hyperuricemia as compared to the control LETO rats (77 vs. 36.1%, P < 0.05), indicating that insulin resistance exacerbates the development of hyperuricemia following high-purine load. Consistent with this observation, improvement of insulin sensitivity by administration of rosiglitazone significantly reduced high-purine diet induced renal injury and gouty-like lesions. It was found that insulin resistance is associated with impaired capability for maintaining the homeostasis of renal uric acid excretion and reabsorption. Upon high-purine load, insulin resistance enhances urate reabsorption as manifested by up-regulated URAT1 expression and reduces urate excretion as characterized by down-regulated UAT expression.

Conclusions

Our data demonstrated strong evidence indicating that insulin resistance acts as an independent risk factor predisposing OLETF rats more susceptible to the development of hyperuricemia and gouty arthritis following high-purine load.

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Acknowledgments

This work was supported by grants from the National Science Foundation of China (NSFC 30470821 to Z. Miao and NSFC 30570890 to C. Li), and partly supported by NIH to C.-Y. Wang.

Conflict of interest statement

The authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Medical School Hospital of Qingdao University, 16 Jiangsu Road, 266003, Qingdao, People’s Republic of China

    Zhimin Miao, Shengli Yan, Jing Wang, Bei Wang, Yujun Li, Xiaoming Xing, Ying Yuan, Dongmei Meng, Luan Wang & Changgui Li

  2. Department of Oral and Maxillofacial Surgery, Mcknight Brain Institute and College of Dentistry, University of Florida, Gainesville, FL, 32610, USA

    Jianguo Gu

  3. Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 1120 15th Street, CA4098, Augusta, GA, 30912, USA

    Shu Zhang & Cong-Yi Wang

  4. Department of Pathology, Medical College of Georgia, 1120 15th Street, Augusta, GA, 30912, USA

    Cong-Yi Wang

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  1. Zhimin Miao
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  2. Shengli Yan
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  4. Bei Wang
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  10. Jianguo Gu
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  11. Shu Zhang
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  12. Changgui Li
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Correspondence to Changgui Li or Cong-Yi Wang.

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Responsible Editor: S. A. Stimpson.

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Miao, Z., Yan, S., Wang, J. et al. Insulin resistance acts as an independent risk factor exacerbating high-purine diet induced renal injury and knee joint gouty lesions. Inflamm. Res. 58, 659–668 (2009). https://doi.org/10.1007/s00011-009-0031-9

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  • DOI: https://doi.org/10.1007/s00011-009-0031-9

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