Fig. 2

Impaired glucose homeostasis in DKO zebrafish and MG-H1 treated larvae. (A) The whole-body glucose was unchanged in DKO larvae compared to WT larvae. n = 7 clutches with 20 larvae. (B) Whole-body glucose was increased in larvae treated with 1 mM MG-H1 compared to the untreated larvae, and it was reduced in larvae co-treated with 1 mM MG-H1 and 10 mM CAR. n = 4 clutches with 20 larvae. (C) Fasting blood glucose in DKO adult zebrafish was elevated compared to WT, GLO1KO and ALDH3A1KO zebrafish, n = 6. (D) 2-hour postprandial blood glucose was increased in DKO zebrafish compared to WT. n = 5. (E–G) The upregulated gluconeogenesis and downregulated glycolysis in DKO larvae and larvae treated with MG-H1 and BOR, n = 4. (H–J) The relative expression levels of key genes responsible for gluconeogenesis and glycolysis in liver and muscle tissues, n = 4. mRNA expression levels were quantified by RT-qPCR and normalized to arnt2. (K) Pyruvate kinase activity in DKO larvae was significantly decreased compared to WT. n = 4. The bars indicate mean ± SD values. Statistical analysis was applied by Student's t-test or one-way ANOVA, ns = not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, significantly different from the WT group; #p < 0.05, significantly different from the single knockout group. MG-H1, methylglyoxal-derived hydroimidazolone 1; BOR, bortezomib; CAR, L-Carnosine; arnt2, aryl hydrocarbon receptor nuclear translocator 2; fbp1a, fructose-1,6-bisphosphatase 1a; pck1, phosphoenolpyruvate carboxykinase 1; g6pc1a.1, glucose-6-phosphatase catalytic subunit 1a; gck, glucokinase; hk1, hexokinase 1; hk2, hexokinase 2; pfkla, phosphofructokinase, liver a; pklr, pyruvate kinase L/R; pfkma, phosphofructokinase, muscle a.