Resveratrol Protects against Methylglyoxal-Induced Hyperglycemia and Pancreatic Damage In Vivo

Abstract

Methylglyoxal (MG) has been found to cause inflammation and insulin resistance in vitro and in vivo in recent studies. Resveratrol has been proposed as an effective treatment that helps lower the risk of developing complications of diabetes. To study the significance of glycosylation-related stress on the pathology of diabetes, the effects of resveratrol were examined in a mouse model of diabetes induced by MG. Resveratrol was given via oral gavage in MG-treated mice, and diabetes-related tests and markers were assessed using biochemical and immunohistochemical analyses. Treatment with resveratrol markedly improved blood glucose level from the oral glucose tolerance test and promoted nuclear factor erythroid 2-related factor-2 (Nrf2) phosphorylation (p < 0.05) in the pancreas of MG-treated mice. However, these effects were abolished by retinoic acid, Nrf2 inhibitor, in resveratrol and retinoic acid-treated and MG-induced mice. These findings support that resveratrol may be useful in the treatment of type-2 diabetes by protecting against pancreatic cell dysfunction.

Resveratrol: A miraculous natural compound for diseases treatment

“…In another in vivo study conducted by Cheng et al., it has been shown that resveratrol promoted nuclear factor erythroid 2‐related factor‐2 (Nrf2) phosphorylation, in the pancreas of methylglyoxal‐treated mice. This finding supports that resveratrol may be useful in the treatment of type 2 diabetes by protecting against pancreatic cell dysfunction (Cheng, Cheng, Lee, Chung, & Chang, 2015). Oxidative stress is also another factor leading to β‐cell failure in type 2 diabetes, and according to animal investigations, RSV decreases the antioxidant damage of β‐cells.…”

The impact of resveratrol on toxicity and related complications of advanced glycation end products: A systematic review

“…Two studies have proposed that the antioxidant capacity of RSV is a possible mechanism for the suppression of AGE toxicity. Cheng et al showed that RSV exerts a protective effect against elevated levels of blood sugar and oxidative stress by activating Nrf 2 in the pancreases of MGO‐treated mice . Lee et al examined the antioxidant effect of RSV in CML‐treated mice.…”

“…Minakawa et al showed that a diet supplemented with RSV protected β‐cells against AGE‐induced oxidative stress and apoptosis in diabetic mice . Supplementation of mice with 10 mg/kg/d of RSV for 12 weeks suppressed the expression of CML‐mediated C/EBPb, and activated Nrf2 which led to improved insulin secretion and attenuated oxidative stress, inflammatory cytokines, and insulin resistance . However, another study did not observe any differences in HMGB1 signaling after 2 weeks of supplementation of 20 mg/kg of RSV in mice with atopic dermatitis …”

“…Cheng et al demonstrated that treatment of MGO cells incubated with RSV stimulates the ERK‐Nrf 2 signaling cascade and elevates the expression of antioxidant enzymes, such as heme oxygenase‐1, which reduced oxidative stress . Cheng et al confirmed the beneficial effects of RSV on Nrf 2 and oxidative stress in animal models . Lee et al exposed mice to CML, treated them with RSV, and noticed that RSV increased the expression of Nrf 2 to attenuate oxidative stress in CML‐injected mice .…”

“…Ohtsu et al indicated that RSV inhibits AGE‐induced IL‐6 production and differentiation of macrophages into the M1 phenotype . Additionally, administration of RSV was shown to alleviate the expression of TNF‐α and IL‐1β in the liver of MGO‐treated mice . AGEs may activate the IKK‐IκBa‐NF‐κB and JNK/ERK‐activator protein‐1 (AP‐1) signaling pathways, which are critical to inducible nitric oxide synthase‐nitric oxide (iNOS‐NO), COX‐2‐PGE2, and matrix metalloproteinase‐13 (MMP) production .…”