Cited by 187Sirtuins and Resveratrol in MedicineAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

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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 Fang Yung·2014·International Journal of Sport Nutrition and Exercise Metabolism

DOI 10.1123/ijsnem.2013-0045

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Abstract

OBJECTIVES: The primary aims of the study were to examine the effect of resveratrol on skeletal muscle SIRT1 expression and energy expenditure in subjects with Type 2 diabetes mellitus (T2DM). BACKGROUND: Animal and in vivo studies indicate that resveratrol increases SIRT1 expression that stimulates PGC1α activity. Subsequent upregulation of AMPK and GLUT4 expression are associated with improved insulin sensitivity in peripheral tissues. METHODS: Ten subjects with T2DM were randomized in a double-blind fashion to receive 3g resveratrol or placebo daily for 12 weeks. Secondary outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure, physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels, and insulin sensitivity. RESULTS: There was a significant increase in both SIRT1 expression (2.01 vs. 0.86 arbitrary units [AU], p = .016) and p-AMPK to AMPK expression ratio (2.04 vs. 0.79 AU, p = .032) in the resveratrol group compared with the placebo group. Although the percentage of absolute change (8.6 vs. -13.9%, p = .033) and percentage of predicted resting metabolic rate (RMR; 7.8 vs. -13.9%, p = .013) were increased following resveratrol, there was a significant reduction in average daily activity (-38 vs. 43.2%, p = .028) and step counts (-39.5 vs. 11.8%, p = .047) when compared with placebo. CONCLUSIONS: 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.

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BackgroundInfluential
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Cao, M., Lu, X., Liu, G., Su, Y., Li, Y., & Zhou, J. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5400 · Cited by 48
“Furthermore, the results of an in vivo study indicated that RSV increases SIRT1 expression and stimulates PGC-1a activity in skeletal muscle (24).”
Retracted
Resveratrol Counteracts Insulin Resistance—Potential Role of the Circulation
Wong, R. H. X., & Howe, P. R. C. (2018) · Nutrients · doi:10.3390/nu10091160 · Cited by 47
“The mechanisms through which resveratrol may improve insulin sensitivity in T2DM are complex, encompassing reduced adiposity and changes in gene expression and activity of key enzymes [19,23].”
BackgroundInfluential
Effects of Resveratrol on Metabolic Indicators in Patients with Type 2 Diabetes: A Systematic Review and Meta‐Analysis
Gu, W., Geng, J., Zhao, H., et al. (2022) · International Journal of Clinical Practice · doi:10.1155/2022/9734738 · Cited by 43
“*e eligible studies included seven studies conducted in Iran [19–25], three studies reported from China [26–28], two studies reported from India [29, 30], and one study each performed in Australia [31], Egypt [32], Netherlands [33], Singapore [34], Japan [35], Spain [36], and Italy [37].”
Coadjuvants in the Diabetic Complications: Nutraceuticals and Drugs with Pleiotropic Effects
Pereira, T. D. M. C., Pimenta, F. S., Porto, M. L., Baldo, M. P., Campagnaro, B. P., Gava, A. L., Meyrelles, S. S., & Vasquez, E. C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081273 · Cited by 43
“[138] showed improvement of insulin sensitivity via SIRT1 through 3000 mg of resveratrol for 12 weeks in type-2 diabetic patients.”
Background
Targeting Abdominal Obesity and Its Complications with Dietary Phytoestrogens
Kuryłowicz, A., Cakala, M., & Puzianowska‐Kuźnicka, M. (2020) · Nutrients · doi:10.3390/nu12020582 · Cited by 43
In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins
Kuryłowicz, A. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17040572 · Cited by 43
Resveratrol for patients with chronic obstructive pulmonary disease
Beijers, R. J. H. C. G., Gosker, H. R., & Schols, A. M. W. J. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000444 · Cited by 41
Hypoglycemic Effect of Resveratrol: A Systematic Review and Meta-Analysis
García-Martínez, B. I., Ruíz-Ramos, M., Pedraza‐Chaverrí, J., Santiago‐Osorio, E., & Mendoza-Núñez, V. M. (2021) · Antioxidants · doi:10.3390/antiox10010069 · Cited by 38
“(2014) [34] RCT double-blind 3 g/day 12 weeks 10 subjects with T2DM 56 ± 6 Glucose and insulin levels, HbA1c, HOMA-IR Tendency of a decrease in HbA1c, no significant changes in insulin sensitivity”
Peripheral targets in obesity treatment: a comprehensive update
Chatzigeorgiou, A., Kandaraki, E., Papavassiliou, A. G., & Koutsilieris, M. (2014) · Obesity Reviews · doi:10.1111/obr.12163 · Cited by 44
Influence of Age and Dose on the Effect of Resveratrol for Glycemic Control in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis
García-Martínez, B. I., Ruíz-Ramos, M., Pedraza‐Chaverrí, J., Santiago‐Osorio, E., & Mendoza-Núñez, V. M. (2022) · Molecules · doi:10.3390/molecules27165232 · Cited by 41
“Published data included in review (n = 11) IRCT2016100716876N2, NCT02704494 (Sattarinezhad, 2019) [35], IRCT2015080223336N2 (Khodabandehloo, 2018) [30], IRCT2015072523336N1 (Seyyedebrahimi, 2018) [31], IRCT2015012420765N1 (Javid, 2016) [29], ACTRN12613000717752 (Thazhath, 2016) [39], IRCT201111198129N1 (Movahed, 2013)…”
BackgroundResultInfluential
Effects of resveratrol therapy on glucose metabolism, insulin resistance, inflammation, and renal function in the elderly patients with type 2 diabetes mellitus: A randomized controlled clinical trial protocol
Ma, N., & Zhang, Y. (2022) · Medicine · doi:10.1097/md.0000000000030049 · Cited by 38
“[26] Conversely, our results showed that resveratrol treatment not only decreased inflammation but also improved kidney function and insulin resistance in the elderly patients with type 2 diabetes mellitus A study found that resveratrol supplementation shows the anti-inflammatory effects and regulates energy expenditu…”
Supplementation with high-dose trans-resveratrol improves ultrafiltration in peritoneal dialysis patients: a prospective, randomized, double-blind study
Lin, C., Sun, X., & Lin, A.-X. (2016) · Renal Failure · doi:10.3109/0886022x.2015.1128236 · Cited by 38
Effects of resveratrol, exercises and their combination on Farnesoid X receptor, Liver X receptor and Sirtuin 1 gene expression and apoptosis in the liver of elderly rats with nonalcoholic fatty liver
Hajighasem, A., Farzanegi, P., Mazaheri, Z., Naghizadeh, M., & Salehi, G. (2018) · PeerJ · doi:10.7717/peerj.5522 · Cited by 38
“Similarly, previous studies reported that resveratrol supplement can improve NAFLD through overexpression of Sirt1 and activation of AMPK-alpha pathway (Goh et al., 2014; Wang et al., 2016).”
Background
Activation of AMPK by Medicinal Plants and Natural Products: Its Role in Type 2 Diabetes Mellitus
Francini, F., Schinella, G. R., & Ríos, J.-L. (2018) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557519666181128120726 · Cited by 37
Effect of Resveratrol on Blood Lipid Levels in Patients with Type 2 Diabetes: A Systematic Review and Meta‐Analysis
Zhao, H., Song, A., Zhang, Y., Shu, L., Song, G., & Ma, H. (2018) · Obesity · doi:10.1002/oby.22348 · Cited by 36
“Bias risk assessment outcome The bias risk assessment for the included studies (16-25) is shown in Figure 1.”
Background
The role of resveratrol in diabetes and obesity associated with insulin resistance
Hoca, M., Becer, E., & Vatansever, H. S. (2021) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2021.1893338 · Cited by 38
Nutrigenomics in Regulating the Expression of Genes Related to Type 2 Diabetes Mellitus
Felisbino, K., Granzotti, J. G., Bello-Santos, L., & Guiloski, I. C. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.699220 · Cited by 43
“…Luteolin and genistein can cause acetylation of histone H3 and cause hypermethylation of genes and cause inhibition, as well as resveratrol and folic acid (Han, 2003; Collins et al., 2007; Berner et al., 2011; Vetterli et al., 2011; Goh et al., 2014; Boyanapalli and Kong, 2015; Li et al., 2015).”
Background
Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells
Tshivhase, A. M., Matsha, T. E., & Raghubeer, S. (2024) · Scientific Reports · doi:10.1038/s41598-023-50084-6 · Cited by 38
“7e,f), as shown by previous research 49 .”
Effects of resveratrol supplementation on risk factors of non-communicable diseases: A meta-analysis of randomized controlled trials
Guo, X., Li, J., Tang, J., & Li, D. (2017) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2017.1349076 · Cited by 36
“…Konno et al., 2013; Kumar and Joghee, 2013; Movahed et al., 2013; Poulsen et al., 2013; Anton et al., 2014; Bashmakov et al., 2014; Chachay et al., 2014; Goh et al., 2014; Witte et al., 2014; Chen et al., 2015; Macedo et al., 2015; Heebøll et al., 2016; Thazhath et al., 2016; Zortea et al., 2016).”
BackgroundResultInfluential
Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises
Capozzi, A., Saucier, C., Bisbal, C., & Lambert, K. (2022) · Molecules · doi:10.3390/molecules27196594 · Cited by 37
Acute Treatment of Resveratrol Alleviates Doxorubicin-Induced Myotoxicity in Aged Skeletal Muscle Through SIRT1-Dependent Mechanisms
Sin, T. K., Tam, B. T., Yu, A. P., Yip, S. P., Yung, B. Y., Chan, L., Wong, S. C. C., Rudd, J. A., & Siu, P. M. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glv175 · Cited by 33
A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy
Nyambuya, T. M., Nkambule, B. B., Mazibuko-Mbeje, S. E., Mxinwa, V., Mokgalaboni, K., Orlando, P., Silvestri, S., Louw, J., Tiano, L., & Dludla, P. V. (2020) · Molecules · doi:10.3390/molecules25235645 · Cited by 34
“, 2014 [39] Singapore Total = 10 (n = 5 controls/n = 5 intervention) Average = 56 (100%) T2D patients, oral hypoglycemic agents, received resveratrol at a dose of 3 g or placebo for 3 months Resveratrol regulated energy expenditure through increased skeletal muscle NAD-dependent deacetylase sirtuin-1 (SIRT1) and 5′ AM…”
Background
The interplay between lipid and Aβ amyloid homeostasis in Alzheimer’s Disease: risk factors and therapeutic opportunities
García‐Viñuales, S., Sciacca, M. F. M., Lanza, V., Santoro, A. M., Grasso, G., Tundo, G. R., Sbardella, D., Coletta, M., Grasso, G., Rosa, C. L., et al. (2021) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2021.105072 · Cited by 34
Nuclear receptors and AMPK: can exercise mimetics cure diabetes?
Wall, C. E., Yu, R. T., Atkins, A. R., Downes, M., & Evans, R. M. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0073 · Cited by 32
Effects of long-term resveratrol-induced SIRT1 activation on insulin and apoptotic signalling in aged skeletal muscle
Sin, T. K., Yu, A. P., Yung, B. Y., Yip, S. P., Chan, L., Wong, S. C. C., Rudd, J. A., & Siu, P. M. (2015) · Acta Diabetologica · doi:10.1007/s00592-015-0767-3 · Cited by 32
“Previous studies have unravelled that resveratrol dose-dependently increased glucose uptake in L6 myotubes in the absence of insulin stimulation [25] and the expression of SIRT1 and GLUT4 was concomitantly increased in the skeletal muscle of type 2 diabetic patients supplemented with resveratrol [26].”
Background
Implications of Resveratrol on Glucose Uptake and Metabolism
León, D., Uribe, E. A., Zambrano, Á., & Salas, M. (2017) · Molecules · doi:10.3390/molecules22030398 · Cited by 35
“A clinical study on a cohort of 10 male diabetic patients revealed that a 12-week RSV treatment induced the upregulation of GLUT4 by AMPK phosphorylation in skeletal muscle [37], revealing one of the putative molecular targets that may induce the observed antidiabetic effects of RSV.”
Background
Precision Nutrition to Activate Thermogenesis as a Complementary Approach to Target Obesity and Associated-Metabolic-Disorders
Reguero, M., de Cedrón, M. G., Wagner, S., Reglero, G., Quintela, J. C., & de Molina, A. R. (2021) · Cancers · doi:10.3390/cancers13040866 · Cited by 32
“[212] Resveratrol Part of a randomized, double-blind, parallel group trial (10 men T2DM 12 wk 2 g/d) No changes in BMI, AT mass ↑ resting EE, SIRT1, AMPK expression in muscle”
Background
The effects of resveratrol on glycemic control and cardiometabolic parameters in patients with T2DM: A systematic review and meta-analysis
Abdelhaleem, I. A., Brakat, A. M., Adayel, H. M., Asla, M. M., Rizk, M. A., & Aboalfetoh, A. Y. (2021) · Medicina Clínica · doi:10.1016/j.medcli.2021.06.028 · Cited by 30
Effects of Functional Phenolics Dietary Supplementation on Athletes’ Performance and Recovery: A Review
Gonçalves, A. C., Gaspar, D., Flores‐Félix, J. D., Falcão, A. C., Alves, G., & Silva, L. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094652 · Cited by 33
“It was also reported that its supplementation (3 g/day) for 12 weeks increased skeletal muscle SIRT1 expression and energy expenditure by upregulating AMPK expression in patients with type 2 diabetes mellitus [170].”
Background
Resveratrol, a Multitasking Molecule That Improves Skeletal Muscle Health
Toniolo, L., Concato, M., & Giacomello, E. (2023) · Nutrients · doi:10.3390/nu15153413 · Cited by 30
“In turn, mitochondrial activity and PGC-1-alpha modulation have been demonstrated to be strictly associated with better fatty acid oxidation and lipid metabolism [7].”
BackgroundInfluential
Bioactive Plant Metabolites in the Management of Non-Communicable Metabolic Diseases: Looking at Opportunities beyond the Horizon
Prasad, C., Imrhan, V., Juma, S., Maziarz, M., Prasad, A., Tiernan, C., & Vijayagopal, P. (2015) · Metabolites · doi:10.3390/metabo5040733 · Cited by 28
“Resveratrol consumption (1000 mg/d for 45 days) significantly lowered fasting glucose, insulin concentrations, hemoglobin A-1c levels, and insulin sensitivity (HOMA-IR) in subjects with type 2 diabetes [89].”
Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: A review of clinical trials
Rezaeiamiri, E., Bahramsoltani, R., & Rahimi, R. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.02.006 · Cited by 28
A comprehensive insight into the potential effects of resveratrol supplementation on SIRT-1: A systematic review
Najafi, M., Nikpayam, O., Tavakoli‐Rouzbehani, O. M., Papi, S., Bioky, A. A., Ahmadiani, E. S., & Sohrab, G. (2021) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2021.102224 · Cited by 27
Resveratrol supplementation and plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials
Sartang, M. M., Mazloom, Z., Sohrabi, Z., Sherafatmanesh, S., & Barati‐Boldaji, R. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.01.012 · Cited by 26

Authors: Goh, K. P., Lee, H. Y., Lau, D. P., Supaat, W., Chan, Y. H., & Koh, A. F. Y.
Affiliations: Khoo Teck Puat Hospital (SG)
ORCID: Lau, Dawn Pingxi
Chan, Yiong Huak
Venue: International Journal of Sport Nutrition and Exercise Metabolism
Publisher: Human Kinetics
Published: 2014-02
Volume: 24
Issue: 1
Pages: 2-13
ISSN: 1526-484X (ISSN-L)
1543-2742
DOI: 10.1123/ijsnem.2013-0045
OpenAlex: W2103667012
Cited by: 187
References: 0
Citations by year: 2026: 8 · 2025: 14 · 2024: 12 · 2023: 20 · 2022: 15 · 2021: 24 · 2020: 22 · 2019: 9 · 2018: 17 · 2017: 17 · 2016: 9 · 2015: 10 · 2014: 10
FWCI: 7.81
Type: journal article
Language: en
Open access: closed
Locations: International Journal of Sport Nutrition and Exercise Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Medical Research Council
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: resveratrol, type 2 diabetes, SIRT1, AMPK, skeletal muscle, energy expenditure, resting metabolic rate, insulin sensitivity, GLUT4, PGC-1α, physical activity, adiponectin, HbA1c
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Resveratrol, Basal Metabolism, Diabetes Mellitus, Type 2, Double-Blind Method, Energy Metabolism, Physical Exertion, Humans, Insulin Resistance, Male, Middle Aged, Plant Extracts, Rest, Stilbenes, Transcription Factors, Exercise, Muscle, Skeletal, Vitis, Glucose Transporter Type 4, AMP-Activated Protein Kinases, Sirtuin 1

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

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