Effects of Resveratrol in Patients with Type 2 Diabetes Mellitus on Skeletal Muscle SIRT1 Expression and Energy Expenditure

Goh, Kian Peng; Lee, Hwei Yee; Lau, Dawn Pingxi; Supaat, Wilma; Chan, Yiong Huak; Koh, Angela

doi:10.1123/ijsnem.2013-0045

Cited by 157 publications

(138 citation statements)

References 24 publications

(30 reference statements)

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“…These data were similar to those obtained from a previous study (11) and support the use of RSV as a potential glucose-lowering agent in T2DM. Furthermore, the results of an in vivo study indicated that RSV increases SIRT1 expression and stimulates PGC-1a activity in skeletal muscle (24). The results of the present study demonstrate that RSV is able to mitigate the STZ-induced inhibition of SIRT1, PGC-1α and FOXO3a, which is in accordance with previous results (25)(26)(27).…”

Section: Discussionsupporting

confidence: 92%

Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via Sirtuin type 1

Cao

Liu

et al. 2017

Exp Ther Med

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Abstract. The rising incidence of type 2 diabetes mellitus (T2DM) is a major public health problem and novel therapeutic strategies are required to prevent and treat T2DM. It has been demonstrated that resveratrol (RSV) may prevent T2DM by targeting Sirtuin type 1 (SIRT1), indicating that SIRT1 may be a novel therapeutic target for T2DM prevention. In the present study, a T2DM rat model was established by administering a high fat diet and streptozotocin (STZ) injections. Measurements of blood glucose and insulin confirmed successful establishment of the T2DM model. RSV was used to treat rats with STZ-induced T2DM and the results indicated that RSV reversed the STZ-induced downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α, SIRT1 and forkhead box protein O 3a. Furthermore, RSV modulated the activity of superoxide dismutase and malondialdehyde, which are associated with oxidative stress. In vitro, cells from the insulinoma cell line clone 1E were pretreated with palmitic acid (PA) to simulate a high fat environment. The results of reverse transcription-quantitative polymerase chain reaction indicated that PA suppressed the expression of SIRT1 in a dose-and time-dependent manner. Furthermore, PA modulated the expression of mitochondrial biogenesis-associated, lipid metabolism-associated and β-cell-associated genes, whereas RSV treatment ameliorated the PA-induced changes in the expression of these genes via SIRT1. The results of the present study suggest that RSV participates in the prevention of T2DM by regulating the expression of mitochondrial genes associated with biogenesis, lipid metabolism and β-cells via SIRT1. The results of the current study provide an insight into the mechanisms by which SIRT1 inhibits T2DM and may be used as a basis for future studies.

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Section: Discussionsupporting

confidence: 92%

Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via Sirtuin type 1

Cao

Liu

et al. 2017

Exp Ther Med

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“…14 In previous studies, the dosage range for trans-resveratrol is about 10-3000 mg/d irrespective of the renal function. [15][16][17][18] In the present study, 150 and 450 mg/d transresveratrol were chosen as the two doses were suggested to be safe yet effective and tolerant enough. 19,20 We did not find any resveratrol-related adverse events, and the patients were well-tolerated at both doses.…”

Section: Participants and Methodsmentioning

confidence: 99%

Supplementation with high-dose trans-resveratrol improves ultrafiltration in peritoneal dialysis patients: a prospective, randomized, double-blind study

2016

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Background Ultrafiltration (UF) failure mostly contributes to technical failure in peritoneal dialysis (PD) patients, and one of its responsible factors is peritoneal angiogenesis. Resveratrol has been proposed to have an angiogenesis-ameliorating effect on tumor patients. We hypothesize transresveratrol has beneficial effects on angiogenesis-related markers in PD patients. Methods In this prospective, randomized, and double-blind trial, 72 patients were randomly assigned to 12-week treatment of low-dose or high-dose (150 or 450 mg/d) trans-resveratrol or a placebo. Visits were scheduled at 0, 4, 8, and 12 weeks after treatment. Clinical indices including 24-hour UF volume, UF rate, 24-hour urine volume, residual renal function, and dialysis adequacy (kt/v) were measured. Angiogenesis markers including vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1), angiopoietin-2 (Ang-2), tyrosine kinase 2 (Tie-2), and thrombospondin-1 (Tsp-1) in peritoneal effluent were also assessed by enzyme-linked immunosorbent assay. Results Finally, 64 out of 72 patients were analyzed, 18 in the high-dose group, 22 in the low-dose group, and 24 in the placebo group. Over the 12-week period, patients in the high-dose group [mean change from baseline (95% CI): 171.4 (141.3-201.5) (mL), p ¼ 0.003 (Net UF); 11.3(10.5-12.1) (mL/h), p ¼ 0.02 (UF rate)] or the low-dose group [mean change from baseline (95% CI: 98.1 (49.5-146.7) (mL), p ¼ 0.007 (Net UF); 6.5 (4.4-8.6) (mL/h), p ¼ 0.04 (UF rate)] versus the placebo group had a significantly greater improvement in mean net UF volume and UF rate. The appearance rates of VEGF, Flk-1, and Ang-2 were more significantly reduced (appearance rates of Tie-2 and Tsp-1 increased) in the high-dose group versus the placebo group, but not in the low-dose group. Conclusion Supplementation with trans-resveratrol is beneficial to improve ultrafiltration in PD patients, and high-dose supplementation may improve ultrafiltration by ameliorating angiogenesis induced by conventional lactate-buffered PD solutions.

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“…While resveratrol increases basal glucose uptake in L6 myotubes in a dose-dependent manner [46], the skeletal muscle of diabetic patients exhibits increased expression of SIRT1 and GLUT4 in response to a 12-week daily supplementation with resveratrol [47]. It has also been reported that a 16-month supplementation with resveratrol increased glucose uptake in insulin-stimulated muscles [16] and membrane localization of GLUT4 in the diabetic heart was improved in response to 5 days of resveratrol feeding [48].…”

Section: Resveratrol May Confer Anti-hyperglycemic Effects Through Momentioning

confidence: 99%

Modulation of SIRT1-Foxo1 Signaling axis by Resveratrol: Implications in Skeletal Muscle Aging and Insulin Resistance

Sin

Yung

Siu

2015

Cell Physiol Biochem

119

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Aging individuals and diabetic patients often exhibit concomitant reductions of skeletal muscle mass/strength and insulin sensitivity, suggesting an intimate link between muscle aging and insulin resistance. Foxo1, a member of the FOXO transcription factor family, is an important player in insulin signaling due to its inhibitory role in glucose uptake and utilization in skeletal muscle. Phosphorylation of Foxo1 is thought to mitigate the transactivation of pyruvate dehydrogenase lipoamide kinase 4 (PDK4), which is a negative regulator of the glycolytic enzyme pyruvate dehydrogenase (PDH). In contrast, how aging would regulate acetylation/deacetylation machineries and glucose utilization in skeletal muscle through the Foxo1/PDH axis remains largely undetermined. Accumulating body of evidence have shown that resveratrol, a natural polyphenol in grapes and red wine, activates the longevity-related protein sirtuin 1 (SIRT1) and augments insulin sensitivity in addition to its well-documented effects on mitochondrial energetics. The present review summarizes the role of Foxo1/SIRT1 in insulin signaling in skeletal muscle and proposes the insight that activation of SIRT1 deacetylase activity to deacetylate and suppress the Foxo1-induced transactivation of PDK4 may represent an anti-hyperglycemic mechanism of resveratrol in aging skeletal muscle.

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Effects of Resveratrol in Patients with Type 2 Diabetes Mellitus on Skeletal Muscle SIRT1 Expression and Energy Expenditure

Abstract: In patients with T2DM, treatment with resveratrol regulates energy expenditure through increased skeletal muscle SIRT1 and AMPK expression. These findings indicate that resveratrol may have beneficial exercise-mimetic effects in patients with T2DM.

Cited by 157 publications

References 24 publications

Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via Sirtuin type 1

Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via Sirtuin type 1

Supplementation with high-dose trans-resveratrol improves ultrafiltration in peritoneal dialysis patients: a prospective, randomized, double-blind study

Modulation of SIRT1-Foxo1 Signaling axis by Resveratrol: Implications in Skeletal Muscle Aging and Insulin Resistance

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