Red wine consumption improves insulin resistance but not endothelial function in type 2 diabetic patients

Napoli, Raffaele; Cozzolino, Domenico; Guardasole, Vincenzo; Angelini, Valentina; Zarra, Emanuela; Matarazzo, Margherita; Cittadini, Antonio; Saccà, Luigi; Torella, Roberto

doi:10.1016/j.metabol.2004.09.010

Cited by 85 publications

(67 citation statements)

References 49 publications

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“…The dose of RSV applied in our study was 1 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 (in vivo) and 0.1-0.3 mol/l (in vitro), which can possibly be achieved by oral red wine consumption. Recently, it was demonstrated that a 2-week consumption of red wine (360 ml/day) substantially attenuates insulin resistance in type 2 diabetic patients (35). The calculated maximal concentration of RSV (red wine contains 0.1-14.3 mg/l trans-RSV) in the above case is ϳ73 g/kg.…”

Section: Discussionmentioning

confidence: 95%

Activation of Estrogen Receptor Is Crucial for Resveratrol-Stimulating Muscular Glucose Uptake via Both Insulin-Dependent and -Independent Pathways

et al. 2008

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OBJECTIVE-Estradiol (E 2 ) is known to modulate insulin sensitivity and, consequently, glucose homeostasis. Resveratrol (RSV), an agonist of estrogen receptor (ER), has exerted antihyperglycemic effects in streptozotocin-induced type 1 diabetic rats in our previous study and was also shown to improve insulin resistance in other reports. However, it remains unknown whether activation of ER is involved in the metabolic effects of RSV via insulin-dependent and -independent mechanisms. RESEARCH DESIGN AND METHODS-MaleSprague-Dawley rats were given a high cholesterol-fructose (HCF) diet for 15 weeks and were treated with RSV for either 15 days or 15 weeks.RESULTS-Here, we show that RSV shifts the metabolic characteristics of rats on an HCF diet toward those of rats on a standard diet. RSV treatment increased insulin-stimulated wholebody glucose uptake and steady-state glucose uptake of soleus muscle and liver in HCF-fed rats as well as enhanced membrane trafficking activity of GLUT4 and increased phosphorylation of insulin receptor in insulin-resistant soleus muscles. Interestingly, the phosphorylated ER level in insulin-resistant soleus muscle was significantly elevated in rats with RSV treatment in both basal and euglycemic-hyperinsulinemic conditions. RSV exerted an insulin-like stimulatory effect on isolated soleus muscle, epididymal fat and hepatic tissue, and C2C12 myotubes. The RSV-stimulated glucose uptake in C2C12 myotubes was dependent on extracellular signal-related kinase/p38 (early phase, 1 h) and p38/phosphoinositide 3-kinase (late phase, 14 h) activation. Inhibition of ER abrogated RSV-induced glucose uptake in both early and late phases.CONCLUSIONS-Collectively, these results indicate that ER is a key regulator in RSV-stimulating insulin-dependent and -independent glucose uptake, which might account for the protective effects of RSV on diet-induced insulin resistance syndrome.

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Section: Discussionmentioning

confidence: 95%

Activation of Estrogen Receptor Is Crucial for Resveratrol-Stimulating Muscular Glucose Uptake via Both Insulin-Dependent and -Independent Pathways

et al. 2008

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“…The exact mechanisms behind the metabolic syndrome are not known, but a major culprit seems to be reduction of the metabolic effects of insulin, denoted insulin resistance (2). Results of prospective randomized trials with a duration up to a few months have suggested that intake of moderate amounts of alcohol induces an increase of HDL cholesterol levels (3,4) and also reduces insulin resistance (5), while acute effects of alcohol intake are also related to vasodilation leading to lowered blood pressure. Thus, moderate alcohol intake seems to counteract many components of the metabolic syndrome, perhaps even the insulin resistance itself.…”

Section: Introductionmentioning

confidence: 99%

Effects of moderate red wine consumption on liver fat and blood lipids: a prospective randomized study

Kechagias¹,

Zanjani²,

Gjellan³

et al. 2011

Annals of Medicine

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Methods: Thirty-two healthy women and 12 healthy men (34±9 years of age) were randomized to consume 150 ml of red wine/day for women (16g ethanol/d) or the double amount for men (33g ethanol/d), or to alcohol abstention during 90 days.Participants underwent proton-nuclear magnetic-resonance spectroscopy for measurement of hepatic triglyceride content (HTGC). Blood samples for assessment of cardiovascular risk were drawn before and after the intervention.Results: After exclusion of three subjects with steatosis at baseline a trend towards increased HTGC was apparent by red wine (before median: 1.1%, range 0.2-3.9%, after median: 1.1%, range 0.5-5.2 %, p=0.059) a difference that was statistically significant compared with abstainers (p=0.02). However, no subject developed hepatic steatosis.LDL-cholesterol was lowered by red wine (-0.3 mmol/l, SE -0.1, 95% CI -0.6 to -0.04). Conclusions:Moderate consumption of red wine during three months increased HTGC in subjects without steatosis at baseline. However, since not a single participant developed steatosis we suggest that the threshold of alcohol consumption to define nonalcoholic fatty liver disease should not be lower than the amount in our study.  The results of this study provide original information about the effect of moderate wine drinking on the hepatic triglyceride content.

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“…11) However, the consumption of RV failed to affect vascular reactivity and NO production in DM patients. 12) In addition, the major upstream effectors of the eNOS pathway include Akt. 13) Evidence from our previous experimental data indicates that clonidine promotes the Akt/eNOS pathway, but it inhibits the pathway in the diabetic aorta.…”

mentioning

confidence: 99%

Resveratrol Ameliorates Clonidine-Induced Endothelium-Dependent Relaxation Involving Akt and Endothelial Nitric Oxide Synthase Regulation in Type 2 Diabetic Mice

Taguchi

Hida

Matsumoto

et al. 2015

Biological & Pharmaceutical Bulletin

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Diabetic vascular complication is one of the manifestations of endothelial dysfunction. Resveratrol (RV)is considered to be beneficial in protecting endothelial function. However, the exact protective effect and mechanisms involved have not been fully clarified. In this study, we investigated the relationship between Akt/endothelial nitric oxide synthase (eNOS) activation and RV in diabetes-induced endothelial dysfunction. Aortas were dissected and placed in organ chambers, and nitric oxide (NO) production in response to acetylcholine (ACh) and RV was measured. ACh-induced endothelium-dependent relaxation was markedly increased in controls by RV pretreatment. Furthermore, RV caused NO-dependent relaxation via the Akt signaling pathway, which was weaker in the aortas of diabetic mice than age-matched controls. To further examine the underlying mechanisms, we measured the phosphorylation of Akt and eNOS by Western blotting. RV caused the phosphorylation of Akt and eNOS in aortas, which was decreased in diabetic mice. However, RV augmented the impaired clonidine-induced relaxation in diabetic mice. Interestingly, the phosphorylation of Akt and eNOS was increased under stimulation with RV and clonidine only in diabetic mice. Thus, either RV or clonidine causes Akt-dependent NO-mediated relaxation, which is weaker in diabetic mice than controls. However, additional exposure to RV and clonidine has an augmenting effect on the Akt/eNOS signaling pathway under diabetic conditions. RV-induced Akt/eNOS activity may be a common link involved in the clonidine-induced Akt/eNOS activity, so RV and clonidine may have a synergistic effect. Key words resveratrol (RV); endothelial dysfunction; nitric oxide (NO); AktType 2 diabetes (DM) is associated with several complications, especially vascular complications (e.g., coronary insufficiency, cerebrovascular and peripheral vascular disease), which are the main etiologies leading to morbidity and mortality.1) Patients with DM exhibit complex vascular changes, such as an accelerated atherosclerosis process and hypercoagulability.2) Atherosclerosis is a major factor that accelerates diabetic vascular complications, and vascular endothelial dysfunction is considered to be the earliest detectable abnormality in the process of atherosclerosis.3) Thus, improving vascular endothelial dysfunction plays an important role in diabetic treatment.Resveratrol (RV; 3,5,4′-trihydroxystilbene) is a naturally occurring polyphenolic phytoalexin found in many plants, and it has been shown to prolong the lifespan of lower organisms. 4)Foods and drinks rich in RV, such as Mediterranean diets and French wine, are associated with a reduced risk of cardiovascular mortality in humans, and evidence has confirmed that RV has antiapoptotic, anti-inflammatory, anti-aging, and anticancer effects as well as a cardiovascular protective effect. 5-7)We previously reported that RV increased nitric oxide (NO) production in diabetic mice. 8) However, the underlying mechanisms are complicated and remain unclear.Endotheli...

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Red wine consumption improves insulin resistance but not endothelial function in type 2 diabetic patients

Cited by 85 publications

References 49 publications

Activation of Estrogen Receptor Is Crucial for Resveratrol-Stimulating Muscular Glucose Uptake via Both Insulin-Dependent and -Independent Pathways

Activation of Estrogen Receptor Is Crucial for Resveratrol-Stimulating Muscular Glucose Uptake via Both Insulin-Dependent and -Independent Pathways

Effects of moderate red wine consumption on liver fat and blood lipids: a prospective randomized study

Resveratrol Ameliorates Clonidine-Induced Endothelium-Dependent Relaxation Involving Akt and Endothelial Nitric Oxide Synthase Regulation in Type 2 Diabetic Mice

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