Abstract Title:

Resveratrol attenuates renal hypertrophy in early-stage diabetes by activating AMPK.

Abstract Source:

Am J Nephrol. 2010;31(4):363-74. Epub 2010 Mar 20. PMID: 20332614

Abstract Author(s):

Da-Fa Ding, Na You, Xiao-Mei Wu, Jia-Rong Xu, Ai-Ping Hu, Xiao-Long Ye, Qun Zhu, Xiu-Qing Jiang, Heng Miao, Chao Liu, Yi-Bing Lu

Article Affiliation:

Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, China.

Abstract:

BACKGROUND: Recent studies suggest the involvement of the adenosine monophosphate-activated serine/threonine protein kinase (AMPK) pathway in the pathogenesis of diabetic nephropathy (DN). Resveratrol, an agent that activates AMPK, may have the potential to protect against the development of DN. This study was designed to investigate the therapeutic effects of resveratrol on renal hypertrophy in early-stage diabetes and the underlying mechanisms.

METHOD: Molecular and structural changes involved in the pathogenesis of DN were tested in a rat model of early-stage diabetes. Renal mesangial cells (RMCs) were cultured in media containing different concentrations of glucose with or without resveratrol. Cellular DNA synthesis was assayed by measuring (3)H-thymidine incorporation. The phosphorylation status of AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and phospho- ribosomal protein S6 (S6) was analyzed by Western blot.

RESULTS: Resveratrol reduced plasma creatinine and urinary albumin excretion and attenuated renal hypertrophy without affecting blood glucose levels. Moreover, resveratrol activated AMPK and inhibited phosphorylation of 4E-BP1 and S6 in diabetic rat kidneys. In vitro, resveratrol blocked high glucose-induced dephosphorylation of AMPK and phosphorylation of 4E-BP1 and S6 and strongly inhibited both the DNA synthesis and proliferation of RMCs.

CONCLUSION: These findings suggest the possibility that resveratrol exerts antiproliferative, antihypertrophic effects by activating AMPK and reducing 4E-BP1 and S6 phosphorylation, thus suppressing the development and progression of DN.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Renoprotective : CK(1308) : AC(593)
Additional Keywords : Stilbenes : CK(402) : AC(242)

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