Functional interplay of reactive metabolites in diabetic organ damage in zebrafish

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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.