Inhibition of type 3 iodothyronine deiodinase enhances differentiation of human induced pluripotent stem cells to β cells

Intracellular triiodothyronine (T3) level is up-regulated by type 2 iodothyronine deiodinase (Dio2), which converts thyroxine (T4) to T3, or is down-regulated by type 3 iodothyronine deiodinase (Dio3), which converts T3 to diiodothyronine. β cells derived from human induced pluripotent stem cells (hiPSCs) were examined to investigate the potential roles of deiodinases during differentiation of human pancreatic β cells. hiPSCs were differentiated stepwise over 29 days. The T3 level in the differentiated cells was determined by the T3 supplied to the medium, and the Dio3 in the cells as the differentiation medium contained T3 but not T4. The Dio3 expression significantly changed during the differentiation. Iopanoic acid (IOP), an inhibitor of Dio3 activity, was used to investigate the involvement of Dio3 during differentiation. The proportion of β cells that expressed both C-peptide and NKX6 homeobox 1 that differentiated in the presence of IOP (+IOP) on day (D) 29 (D-29) was significantly higher than that expressed in the absence of IOP (−IOP). The insulin content of differentiated+IOP cells on D-29 was significantly higher than that differentiated−IOP cells. These results suggest that Dio3 inhibition by IOP from D-0 to D-29 enhances the differentiation of hiPSCs to β cells.