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Protective effects of adiponectin on uncoupling of glomerular VEGF–NO axis in early streptozotocin-induced type 2 diabetic rats

  • Nephrology - Original Paper
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Abstract

Purpose

To determine whether adiponectin could reduce microalbuminuria and provide renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular vascular endothelial growth factor (VEGF)–nitric oxide (NO) axis in streptozotocin-induced type 2 diabetic rats.

Methods

Wistar rats were randomly divided into normal control group, diabetic nephropathy (DN) group induced by high-fat feeding and streptozotocin, diabetic rats injected with adenovirus-expressed adiponectin (AD-AdipoQ), and diabetic rats injected with AD-IRES-EGFP as control. Blood and urine samples were collected. Endothelium-dependent vasodilatation (EDV) of the aorta was measured. Renal tissues were collected for CD34 immunohistochemistry. Glomerular NO and VEGF levels were measured by the Griess reaction and Western blot testing, respectively.

Results

Injections of AD-AdipoQ significantly increased serum adiponectin levels and reduced the urinary albumin-to-creatinine ratio in diabetic rats (P < 0.05). The levels of plasma glucose, serum insulin, high-sensitivity C-reactive protein, and malondialdehyde were significantly reduced in diabetic rats after injections of AD-AdipoQ (P < 0.05). Severe EDV impairment was observed in the DN group, which was improved by AD-AdipoQ. CD34 expression in the glomeruli was also higher in diabetic rats, indicating increased proliferation of glomerular endothelial cells. However, AD-AdipoQ improved the increased proliferation of endothelial cells in the glomeruli. Diabetic rats showed increased glomerular VEGF levels and reduced NO levels. This uncoupling of the VEGF–NO axis was partially improved by AD-AdipoQ.

Conclusion

Adiponectin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular VEGF–NO axis in early diabetic nephropathy.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grants NO. 81300688), Weifang Health Bureau Program (2013021), the Science and Technology Innovation Fund of Affiliated Hospital of Weifang Medical University (NO. K12CX1007), and the Science and Technology Innovation Fund of Weifang Medical University (NO. K1302017).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Endocrinology, Affiliated Hospital of Weifang Medical University, No. 2428, Yuhe Road, Weifang, 261031, China

    Ningning Hou, Na Huang, Jiangang Zhao, Xue Liu & Xiaodong Sun

  2. Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China

    Fang Han

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  1. Ningning Hou
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  2. Na Huang
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  3. Fang Han
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  4. Jiangang Zhao
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  5. Xue Liu
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  6. Xiaodong Sun
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Correspondence to Xiaodong Sun.

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Hou, N., Huang, N., Han, F. et al. Protective effects of adiponectin on uncoupling of glomerular VEGF–NO axis in early streptozotocin-induced type 2 diabetic rats. Int Urol Nephrol 46, 2045–2051 (2014). https://doi.org/10.1007/s11255-014-0807-x

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  • DOI: https://doi.org/10.1007/s11255-014-0807-x

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