Grape seed extract supplementation prevents high-fructose diet-induced insulin resistance in rats by improving insulin and adiponectin signalling pathways

Abstract

Recent evidence strongly supports the contention that grape seed extract (GSE) improves hyperglycaemia and hyperinsulinaemia in highfructose-fed rats. To explore the underlying molecular mechanisms of action, we examined the effects of GSE on the expression of muscle proteins related to the insulin signalling pathway and of mRNA for genes involved in the adiponectin signalling pathway. Compared with rats fed on a normal diet, high-fructose-fed rats developed pathological changes, including insulin resistance, hyperinsulinaemia, hypertriacylglycerolaemia, a low level of plasma adiponectin and a high level of plasma fructosamine. These disorders were effectively attenuated in high-fructose-fed rats supplemented with GSE. A high-fructose diet causes insulin resistance by significantly reducing the protein expression of insulin receptor, insulin receptor substrate-1, Akt and GLUT4, and the mRNA expression of adiponectin, adiponectin receptor R1 (AdipoR1) and AMP-activated protein kinase (AMPK)-a in the skeletal muscle. Supplementation of GSE enhanced the expression of insulin signalling pathway-related proteins, including Akt and GLUT4. GSE also increased the mRNA expression of adiponectin, AdipoR1 and AMPK-a. In addition, GSE increased the mRNA levels of glycogen synthase and suppressed the mRNA expression of glycogen synthase kinase-3-a, causing an increase in glycogen accumulation in the skeletal muscle. These results suggest that GSE ameliorates the defective insulin and adiponectin signalling pathways in the skeletal muscle, resulting in improved insulin resistance in fructose-fed rats.

Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome - randomized, cross-over, placebo-controlled study

“…Stull et al, 2010 reported increased insulin sensitivity in obese, non-diabetic, and insulinresistant subjects after 8 weeks blueberry supplementation using the hyperinsulinemic euglycemic clamp procedure [16] and Brasnyó et al showed that resveratrol, a stilbene polyphenol found in red wine, improved insulin sensitivity in human subjects with type II diabetes [33]. Taken collectively, the results of the current study along with the findings from animal studies [18,19] suggests that GSE could improve insulin resistance. However, future studies using conventional insulin clamp procedures are required to confirm this effect [16].…”

“…These effects have also been associated with improvements in insulin sensitivity [16] and postprandial insulin responses [9]. Grape seeds are a concentrated source of polyphenols and have received considerable attention for their antioxidant capacity and biological effects after chronic consumption [17][18][19][20]. In the present study, we tested the hypothesis that acute supplementation with grape seed extract (GSE) would attenuate meal-induced alterations in the oxidant and inflammatory status in men and women with the MetS.…”

Oligomeric Cocoa Procyanidins Possess Enhanced Bioactivity Compared to Monomeric and Polymeric Cocoa Procyanidins for Preventing the Development of Obesity, Insulin Resistance, and Impaired Glucose Tolerance during High-Fat Feeding

“…Both GSE treatments significantly increased plasma adiponectin levels and reduced plasma TAG levels compared to the highfructose control group. Furthermore, a high-fructose diet supplemented with 1% GSE significantly inhibited suppression of GLUT-4 protein expression and increased glycogen accumulation in skeletal muscle compared to the high-fructose control group and both GSE treatments significantly restored mRNA expression of adiponectin levels compared to the positive control 74 . Chronic HF and high-fructose diets can reduce tissues responsiveness to insulin and impair glucose metabolism by down-regulating the expression of insulin-stimulated 22 proteins and mRNA genes involved in insulin signaling.…”

“…The adverse effects of the well-known cytokine TNF-α have been extensively studied and will be described in detail later in this review. Expression of the adipocyte-specific protein adiponectin, helps to modulate FFA catabolism via stimulation of various nuclear receptors thus contributing to lower levels of circulating FFA and glucose 72,74 .…”

“…The oligomerrich treatment significantly reduced mice fasting blood glucose levels, as well as significantly improved mice glucose and insulin tolerances compared to controls 100 . In another study, Wistar rats were administered a high-fructose [63% (w/w)] diet (to induced insulin resistance), and supplemented with either 0.5 or 1% (w/w) GSE for 8 weeks 74 . Both GSE treatments significantly increased plasma adiponectin levels and reduced plasma TAG levels compared to the highfructose control group.…”