甲基乙二醛:肥胖及糖尿病人群的治疗新靶点

Methylglyoxal: a new therapeutic target for obesity and diabetes

甲基乙二醛(MG)是一种高反应性的二羰基化合物,其主要来源于葡萄糖和果糖代谢,也可以来源于食物,是食品添加剂中的一种重要成分。MG可以使蛋白质和DNA反应生成晚期糖基化终末产物(AGEs),具有细胞毒性。MG通过直接的诱发氧化应激反应,使细胞内活性氧簇增加,导致细胞的代谢紊乱与凋亡。在代谢异常和糖尿病患者的体内,这种不正常的二羰基代谢产物的堆积,会引起DNA和蛋白质重构增多,导致细胞和组织功能的失调以及老化与疾病。代谢受损的肥胖及糖尿病患者体内的MG水平明显升高,是代谢紊乱及血管并发症发生的重要危险信号。乙二醛酶系统代谢可以解毒MG,使其转化成无毒的乳酸盐排出体外,不足以产生毒性反应。提高乙二醛酶1的活性可以降解MG并抑制AGEs的产生,达到解毒的作用。通过解毒MG途径,为糖尿病的诊治提供了一条全新的思路。

Methylglyoxal (MG), a highly reactive dicarbonyl compound, is mainly derived from glucose and fructose metabolism, and can also be derived from food, which is an important ingredient in food additives. MG can make protein and DNA react to form advanced glycosylated end products (AGEs), which is cytotoxic. By directly inducing oxidative stress, MG increases intracellular reactive oxygen species, leading to cell metabolic disorders and apoptosis. In patients with metabolic abnormalities and diabetes, the accumulation of this abnormal dicarbonyl metabolite causes an increase in DNA and protein remodeling, leading to dysfunction of cell and tissue functions, aging and disease. In obese patients with impaired metabolism and diabetic patients, MG level is significantly increased, which is an important risk signal for metabolic disorders and vascular complications. The systematic metabolism of glyoxalase can detoxify MG and make it into non-toxic lactate salt to be expelled from the body, which is not enough to produce toxic reaction. Increasing the activity of glyoxalase 1 can degrade MG and inhibit the production of AGEs to achieve detoxification. Through the way of detoxifying MG, it provides a new idea for the diagnosis and treatment for diabetes.