A composition comprising a non-native pancreatic β cell, wherein :(a) the non-native pancreatic β cell comprises one or more crystalline insulin granules； (b) the non-native pancreatic β cell expresses the following genes: INS, PDX1, NKX6-1, and ZNT8； and (c) the non-native pancreatic β cell exhibits an in vitro glucose-stimulated insulin secretion response to a first glucose challenge and a second glucose challenge when the first glucose challenge and the second glucose challenge are applied sequentially is claimed. Methods of preparing such cells using media comprising a thyroid hormone signalling pathway activator such as triiodothyronine and a transforming growth factor b (TGF-b) signalling pathway inhibitor, such as Alk5 inhibitor II are claimed.
