British Journal of Nutrition

Metabolism and Metabolic Studies

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

Pál Brasnyóa1, Gergő A. Molnára1, Márton Mohása1, Lajos Markóa1, Boglárka Laczya1, Judit Cseha1, Esztella Mikolása1, István András Szijártóa1, Ákos Méreia1, Richárd Halmaia1, László G. Mészárosa2, Balázs Sümegia3 and István Wittmanna1 c1

a1 2nd Department of Internal Medicine and Nephrological Center, Faculty of Medicine, University of Pécs, Pacsirta Street 1, Pécs H-7624, Hungary

a2 Life Sciences Foundation, Theoretical Biochemistry Group, Augusta, GA 30909, USA

a3 Department of Biochemistry and Medical Chemistry, Faculty of Medicine, University of Pécs, Pécs H-7624, Hungary

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.

(Received August 25 2010)

(Revised December 07 2010)

(Accepted January 17 2011)

(Online publication March 09 2011)

Correspondence:

c1 Corresponding author: Professor I. Wittmann, fax +36 72 536 051, email istvan.wittmann@aok.pte.hu

Footnotes

Abbreviations: Akt, protein kinase B; CGM, continuous glucose monitoring; GIP, glucose-dependent insulinotropic peptide; GLP-1, glucagon-like peptide 1; HOMAβ, homeostasis model of assessment of β-cell function; HOMAIR, homeostasis model of assessment for insulin resistance; ISI, insulin sensitivity index; MCR, metabolic clearance rate; o-Tyr, ortho-tyrosine; pAkt, phosphorylated protein kinase B

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