Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients

Abstract

OBJECTIVETo assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk.RESEARCH DESIGN AND METHODSThirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR.RESULTSIn the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid–reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs.CONCLUSIONSA natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.

Grape Pomace Aqueous Extract (GPE) Prevents High Fat Diet-Induced Diabetes and Attenuates Systemic Inflammation

“…Accumulating evidence indicates that grape polyphenols work in many different ways to decrease blood glucose [45], improve insulin resistance [46]- [48], suppress hyperinsulinemia [49], and reduce blood pressure and lipid concentration [50]- [53]. Consistently, our results showed that the plasma glucose and insulin mRNA expression was significantly decreased in the non-STZ treated mice fed with GPE.…”

Grape seed proanthocyanidins and metformin act by different mechanisms to promote insulin signaling in rats fed high calorie diet

“…In view of this, the combination of GSP and MET could be a promising and effective treatment for insulin resistance and associated disorders. Future studies involving a preventive protocol with GSP and/or MET to HFFD rats would be useful since in a human study grape polyphenol treatment prevented the development of T2D in first degree relatives of T2D patients (Hokayem et al 2013). …”

Contribution of mitochondria and endoplasmic reticulum dysfunction in insulin resistance: Distinct or interrelated roles?

“…Targeting of mitochondrial ROS appears more relevant for improving glucose homoeostasis, as targeted expression of catalase or manganese superoxide dismutase (MnSOD) to mitochondria has been shown to improve insulin signalling in skeletal muscle and whole-body glucose homoeostasis [12,34]. Thus, it may be more prudent to conclude that mitochondrial dysfunction is most likely not causally involved in the development of muscle IR, although targeting it might be an effective way to improve insulin signalling in skeletal muscle and restore glucose homoeostasis [35].…”