Figure 1

ABCC8-deficient insulin-producing cells exhibited greater insulin secretion and insulin secretion responses to the various stimulations. (A) Schematic of directed differentiation from pluripotent stem cells to insulin-producing cells via the small molecule-based method. (B) Immunofluorescence for insulin at the final stage of differentiation. ABCC8-deficient cells demonstrated similar differentiation efficiency as wild-type cells. (C) ELISA analysis for insulin content in the supernatant. ABCC8-deficient cells demonstrated greater insulin secretion than wild-type cells. (D) ELISA analysis for C-peptide content in the supernatant. ABCC8-deficient cells demonstrated greater C-peptide secretion than wild-type cells. (E) ELISA analysis for C-peptide levels in the presence of vehicle, diazoxide and glimepiride. (F) The fold change of C-peptide content after diazoxide and glimepiride stimulation. Diazoxide and glimepiride decreased and increased C-peptide secretion in wild-type and heterozygous mutated cells, respectively. Neither diazoxide nor glimepiride had an effect on homozygous mutated cells. (G) The fold change of C-peptide content after octreotide, nicorandil and nifedipine treatment. Octreotide, nicorandil and nifedipine decreased insulin secretion in wild-type, heterozygous mutated and homozygous mutated cells. (H) The fold change of C-peptide content after ouabain, extracellular ATP and calcium chloride treatment.