Resveratrol Attenuates Renal Hypertrophy in Early-Stage Diabetes by Activating AMPK

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 ³H-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.

How Can Nanotechnology Be Applied to Sensors for Breath analysis?

“…Activating AMPK can reduce glomerular and renal tubule damage [51]. Reports have demonstrated that Res can alleviate renal damage in earlystage diabetic nephropathy by activating AMPK [52]. Therefore, the AMPK signaling pathway is a protective regulatory mechanism.…”

Autophagy in Chronic Kidney Diseases

“…Recent researches have demonstrated that the occurrence and development of type 2 diabetes and its complications are closely associated with the change of nutrient-sensitive pathways. The major related nutrient-sensitive signal proteins include mTOR [40] , AMPK [41] and oxidized coenzyme-dependent histone deacetylase (Sirt1) [42] . As nutritional conditions change (high glucose environment), nutrient signal pathways inflict damage on the autophagy functions of cells so that the cells are unable to react normally to all sorts of extracellular stress, and organelle functions are further disordered, resulting in diabetic nephropathy.…”

“…Both resveratrol and metformin can be used to activate AMPK. Reports have demonstrated that resveratrol can alleviate renal damage in early-stage diabetic nephropathy by activating AMPK [41] . In the glomeruli and renal tubules in animal models of type 1 and 2 diabetic nephropathy, AMPK activity is inhibited.…”

Autophagy in Kidney Health and Disease

“…In the high glucose milieu, studies showed that AMPK phosphorylation and activity were reduced in the renal cortex of kidneys from STZ-induced diabetic rats and db/ db mice, which are models of type 1 and type 2 diabetes, respectively (9,15,36,46,75,82). AMPK activators, resveratrol (9,15,36), metformin (9,15,36,46,75,82), and 5-aminoimidazole-4-carboxamide-1b-riboside (AICAR) (46) attenuated renal hypertrophy, lipid accumulation and albumin excretion in diabetic kidneys. Thus, inhibition of AMPK activity contributes to alterations in the diabetic kidney, such…”