Functional interplay of reactive metabolites in diabetic organ damage in zebrafish

斑马鱼中乙二醛酶1 （glo1）的缺失只会导致部分甲基乙二醛增加，并伴有葡萄糖耐量受损。ALDH3a1, AKR1a1a, ALDH2.1， ALDH9a1b和ALDH3b1在glo1突变体中代偿上调，它们可以解毒不同的反应性代谢物。通过使用glo1/akr1a1a、glo1/aldh3a1、glo1/aldh2.1双突变体以及aldh9a1b和aldh3b1单突变体，我们现在将测试不同酶群中反应性代谢物的积累，并研究这是如何导致器官损伤的，以及体育锻炼是否会改变酶活性和反应性代谢物的积累。

Loss of glyoxalase1 (glo1) in zebrafish leads to a partial methylglyoxal increase only and was accompanied by an impaired glucose tolerance. ALDH3a1, AKR1a1a, ALDH2.1, ALDH9a1b and ALDH3b1 were compensatory upregulated in glo1 mutants and they can detoxify different reactive metabolites. By using glo1/akr1a1a, glo1/aldh3a1, glo1/aldh2.1 double mutants as well as aldh9a1b and aldh3b1 single mutants, we will now test the accumulation of reactive metabolites in the different enzyme constellation and address how this leads to organ damages and if physical exercise will alter the enzyme activity and accumulation of reactive metabolites.