Skip to main content
×
Home
    • Aa
    • Aa

Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients

  • Pál Brasnyó (a1), Gergő A. Molnár (a1), Márton Mohás (a1), Lajos Markó (a1), Boglárka Laczy (a1), Judit Cseh (a1), Esztella Mikolás (a1), István András Szijártó (a1), Ákos Mérei (a1), Richárd Halmai (a1), László G. Mészáros (a2), Balázs Sümegi (a3) and István Wittmann (a1)...
Abstract

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Professor I. Wittmann, fax +36 72 536 051, email istvan.wittmann@aok.pte.hu
References
Hide All
1 Renaud S & de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339, 15231526.
2 Goldfinger TM (2003) Beyond the French paradox: the impact of moderate beverage alcohol and wine consumption in the prevention of cardiovascular disease. Cardiol Clin 21, 449457.
3 Cucciolla V, Borriello A, Oliva A, et al. (2007) Resveratrol: from basic science to the clinic. Cell Cycle 6, 24952510.
4 Silan C (2008) The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats. Biol Pharm Bull 31, 897902.
5 Ray PS, Maulik G, Cordis GA, et al. (1999) The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med 27, 160169.
6 Palfi A, Bartha E, Copf L, et al. (2009) Alcohol-free red wine inhibits isoproterenol-induced cardiac remodeling in rats by the regulation of Akt1 and protein kinase C alpha/beta II. J Nutr Biochem 20, 418425.
7 Wallerath T, Deckert G, Ternes T, et al. (2002) Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 106, 16521658.
8 Poussier B, Cordova AC, Becquemin JP, et al. (2005) Resveratrol inhibits vascular smooth muscle cell proliferation and induces apoptosis. J Vasc Surg 42, 11901197.
9 Radnai B, Tucsek Z, Bognar Z, et al. (2009) Ferulaldehyde, a water-soluble degradation product of polyphenols, inhibits the lipopolysaccharide-induced inflammatory response in mice. J Nutr 139, 291297.
10 Delbosc S, Paizanis E, Magous R, et al. (2005) Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 179, 4349.
11 Houstis N, Rosen ED & Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440, 944948.
12 Wei Y, Whaley-Connell AT, Chen K, et al. (2007) NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat. Hypertension 50, 384391.
13 Evans JL, Maddux BA & Goldfine ID (2005) The molecular basis for oxidative stress-induced insulin resistance. Antioxid Redox Signal 7, 10401052.
14 Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40, 405412.
15 Rüweler M, Gülden M, Maser E, et al. (2009) Cytotoxic, cytoprotective and antioxidant activities of resveratrol and analogues in C6 astroglioma cells in vitro. Chem Biol Interact 182, 128135.
16 Bhavnani BR, Cecutti A, Gerulath A, et al. (2001) Comparison of the antioxidant effects of equine estrogens, red wine components, vitamin E and probucol on low-density lipoprotein oxidation in postmenopausal women. Menopause 8, 408419.
17 Sharma S, Anjaneyulu M, Kulkarni SK, et al. (2006) Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats. Pharmacology 76, 6975.
18 Kumar A, Kaundal RK, Iyer S, et al. (2007) Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. Life Sci 80, 12361244.
19 Cockcroft DW & Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16, 3141.
20 Nagaretani H, Nakamura T, Funahashi T, et al. (2001) Visceral fat is a major contributor for multiple risk factor clustering in Japanese men with impaired glucose tolerance. Diabetes Care 24, 21272133.
21 Matthews DR, Hosker JP, Rudenski AS, et al. (1985) Homeostasis model assessment: insulin resistance and B-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412419.
22 Stumvoll M, Mitrakou A, Pimenta W, et al. (2000) Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 23, 295301.
23 Molnár GA, Wagner Z, Markó L, et al. (2005) Urinary ortho-tyrosine excretion in diabetes mellitus and renal failure: evidence for hydroxyl radical production. Kidney Int 68, 22812287.
24 Wagner L, Laczy B, Tamaskó M, et al. (2007) Cigarette smoke-induced alterations in endothelial nitric oxide synthase phosphorylation: role of protein kinase C. Endothelium 4, 245255.
25 Chan WH (2005) Effect of resveratrol on high glucose-induced stress in human leukemia K562 cells. J Cell Biochem 94, 12671279.
26 Yen GC, Duh PD & Lin CW (2003) Effects of resveratrol and 4-hexylresorcinol on hydrogen peroxide-induced oxidative DNA damage in human lymphocytes. Free Radic Res 37, 509514.
27 Kanauchi M, Kimura K, Akai Y, et al. (2004) Insulin resistance and pancreatic beta-cell function in patients with hypertensive kidney disease. Nephrol Dial Transplant 19, 20252029.
28 Thirunavukkarasu M, Penumathsa SV, Koneru S, et al. (2007) Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase. Free Radic Biol Med 43, 720729.
29 Rivera L, Morón R, Zarzuelo A, et al. (2009) Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 77, 10531063.
30 Avogaro A, de Kreutzenberg SV & Fadini GP (2008) Oxidative stress and vascular disease in diabetes: is the dichotomization of insulin signaling still valid? Free Radic Biol Med 44, 12091215.
31 Baur JA & Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5, 493506.
32 Perdew GH, Hollingshead BD, Dinatale BC, et al. (2010) Estrogen receptor expression is required for low-dose resveratrol-mediated repression of aryl hydrocarbon receptor activity. J Pharmacol Exp Ther 335, 273283.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 96
Total number of PDF views: 882 *
Loading metrics...

Abstract views

Total abstract views: 1382 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 20th October 2017. This data will be updated every 24 hours.