T1D SC-beta cells express markers found in beta-cells, including NKX6-1 and PDX1, and have global gene expression patterns similar to adult beta-cells. They are functional in vitro and in vivo, responding to glucose challenges by increasing their human insulin release and controlling glucose levels in diabetic mice after transplantation. After exposure to chemical-induced stress, these cells lose expression of beta-cell markers. They also respond to cytokine stress, which can be partially prevented by treatment with Alk5i, and also respond to known anti-diabetic drugs that cause increased insulin secretion. T1D SC-beta cells can be a potential autologous source for cell replacement therapy or useful for drug screening studies.