Skip to main content
. Author manuscript; available in PMC: 2017 Apr 28.
Published in final edited form as: Sci Transl Med. 2017 Feb 15;9(377):eaaf2584. doi: 10.1126/scitranslmed.aaf2584

Fig. 6. Insulin and IGF1 activate cardioprotective signaling pathways and alleviate cytotoxicity in hiPSC-CMs.

Fig. 6

(A) Phosphorylation arrays demonstrating alterations in hiPSC-CM kinase activity after 12 hour IGF1 or insulin treatment. N=3 biological replicate phosphorylation arrays conducted. Data expressed as means ± SEM. Significant differences defined by *P<0.05 calculated by Student’s t-test. We observed a significant increase in phosphorylation of the following protein amino acid residues after IGF1 treatment (P value listed): Akt1/2/3-S473 (0.01), Akt1/2/3-T308 (0.04), GSK3α/β-S21/S9 (0.03), p53-S15 (0.002), p53-S392 (0.02), p53-S46 (0.003), PRAS40-T246 (0.001), TOR-S2448 (0.0001), WNK1-T60 (0.002). We observed a significant increase in phosphorylation of the following protein amino acid residues after insulin treatment (P value listed): Akt1/2/3-S473 (0.01), Akt1/2/3-T308 (0.04), GSK3-α/β-S21/S9 (0.005), p53-S46 (0.04), PRAS40-T246 (0.007), TOR-S2448 (0.01), WNK1-T60 (0.006). (B) Immunofluorescence of hiPSC-CMs treated with sorafenib, regorafenib, or ponatinib at increasing concentrations for 72 hours in the presence of IGF1 or insulin. Calcein-AM stains viable cells. (C) CellTiter-Glo quantification of hiPSC-CM viability with or without IGF1/insulin co-treatment during TKI treatment. N=5 biological replicates conducted. IGF and insulin treatment significantly rescued ponatinib toxicity (P=0.004). Data expressed as means ± SEM.