糖尿病并发症治疗的新靶点甲基乙二醛

Methylglyoxal:a new therapeutic target for diabetic complications

甲基乙二醛(MG)是人体内糖代谢产生的一种毒性副产物,糖屎病患者体内MG显著增加。MG的积累可导致肾病、心血管病、白内障和老化等多种糖尿病并发症。实验证明MG能与氨基酸残基反应,导致蛋白质降解和交联,形成高级糖化终产物(AGEs)。在生理条件下,MG还能修饰核酸,引起碱基变化,进而导致细胞毒性。本文对MG的代谢途径及其蛋白质、核酸和细胞毒性进行综述,探讨通过阻断MG生成或促进其代谢来治疗糖尿病并发症的策略。

Methylglyoxal （MG） is a α-ketoaldehyde and dicarbonyl formed in ceils as a side product of normal glycometabolism. Recent studies have demonstrated that endogenous accumulation of methylglyoxal in the diabetic patients may result in numerous pathogenic processes in vivo, including renal dysfunction, cardiovascular diseases, cataract or aging. An experimental approach provided a clue regarding the interaction of MG with amino acid residues, resulting in a type of advanced glycation endproducts （AGEs） from sugar modifications advanced glycation endproduct formation. Moreover, methylglyoxal induces a crosslink with biological macromolecules （DNA, RNA or proteins） , thus expecting severe cellular toxicity. This paper presents a comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methylglyoxal metabolism and toxicity, and proposing a strategy of treatment of diabetic complications by inhibiting methylglyoxal biosynthesis and facilitating methylglyoxalase metabolism.