(A) Relative glucose levels in 120 hpf ins mutant larvae after 36 hr of treatment with anti-diabetic drugs (dapagliflozin, pioglitazone, metformin) or reported insulin mimetics (MLR1023, Fraxidin) or the Pck1 inhibitor, 3 MPA; mean ± SEM, n = 3–7 replicates. (B) Schematic representation of the screening pipeline: ins mutant larvae were treated with small molecules starting at 84 hpf and free glucose levels measured at 120 hpf. (C) Scatter plot showing relative change in glucose levels upon treatment with 2233 small molecules. X and Y axes represent two replicates performed for each drug, with the dotted purple lines marking 0.9 on each axis. 72 molecules satisfied the pre-specified cut-off. (D) Relative glucose levels at 120 hpf upon treatment of ins mutants with the three hits – ODQ, Vorinostat, and Flutamide; mean ± SEM, n = 6–7 replicates. P values from t-tests.