Laboratory of Physiology, Institute of Biomedical Research in Light and Image (IBILI), Faculty of Medicine of University of Coimbra (FMUC), Coimbra, Portugal.
Nutr Metab Cardiovasc Dis. 2013 Dec;23(12):1223-30. doi: 10.1016/j.numecd.2013.01.005. Epub 2013 Apr 30.
The influence of lifestyle is well documented, especially the diet regime, in the development of type 2 diabetes (T2D) and associated cardiovascular diseases. Diabetic patients have increased risk of suffering cardiac ischemia and impaired response to such accidents. Methylglyoxal (MG) circulates at high concentration in diabetics' blood and is linked to the development of diabetes chronic complications. We propose that besides promoting the cardiovascular disease, MG may also negatively regulate the endogenous cardioprotection pathways after ischemia.
We performed a comparative study between three animal groups: normal Wistar (W), type 2 diabetic non-obese Goto-Kakizaki (GK) and normal rats submitted to MG chronic administration (3 months) with gradually enhanced concentration, up to 75 mg/Kg (WMG). Hearts were submitted to different experimental conditions: control, ischemia and ischemia-reperfusion. Levels of oxidative stress markers, advanced glycation end-products (AGEs) and their receptors (RAGEs) were evaluated. The serine/threonine protein kinase Akt (Akt), crucial for cardiomyocytes recovery after ischemia, and apoptosis markers were also assessed. Levels of MG, systemic and cardiac oxidative stress markers, AGEs and RAGEs were similar in GK and WMG groups. Akt protein was negatively regulated by MG, leading to impaired apoptotic markers.
Chronic MG administration to normal rodents mimicked most diabetic alterations, being associated with the development of cardiovascular disease and the impairment of survival pathways. Our results demonstrate the negative effect of MG rich diet in healthy animals and suggest the potential of methylglyoxal as a therapeutic target in diabetes.
生活方式的影响，尤其是饮食结构，在 2 型糖尿病（T2D）和相关心血管疾病的发展中已有充分记录。糖尿病患者患心肌缺血的风险增加，并且对这种情况的反应受损。在糖尿病患者的血液中，甲基乙二醛（MG）循环浓度较高，与糖尿病慢性并发症的发展有关。我们提出，除了促进心血管疾病外，MG 还可能负调节缺血后的内源性心脏保护途径。
我们在三组动物之间进行了比较研究：正常 Wistar（W）、2 型非肥胖 Goto-Kakizaki（GK）糖尿病大鼠和正常大鼠接受 MG 慢性给药（3 个月），浓度逐渐增加，最高达 75mg/Kg（WMG）。心脏接受不同的实验条件：对照、缺血和缺血再灌注。评估了氧化应激标志物、晚期糖基化终产物（AGEs）及其受体（RAGEs）的水平。丝氨酸/苏氨酸蛋白激酶 Akt（Akt）对缺血后心肌细胞的恢复至关重要，以及细胞凋亡标志物也进行了评估。MG、全身和心脏氧化应激标志物、AGEs 和 RAGEs 的水平在 GK 和 WMG 组之间相似。MG 负调控 Akt 蛋白，导致细胞凋亡标志物受损。
MG 对正常啮齿动物的慢性给药模拟了大多数糖尿病的改变，与心血管疾病的发生和存活途径的受损有关。我们的结果表明富含 MG 的饮食对健康动物有负面影响，并提示甲基乙二醛作为糖尿病治疗靶点的潜力。
