Type 1 diabetes can potentially be treated by either complete or partial conversion of non-beta cell types in the body to glucose-responsive, insulin secreting cell type or by transplanting either stem cells or non-stem cells re-specified to produce insulin. The early pancreatic development transcription factors Pdx 1 and Ngn3 along with the beta cell differentiation factor MafA have been reported to reprogram exocrine pancreas into insulin producing cells. Using this combination of transcription factors, in our present studies we have reversed the diabetic state of streptozotocin-treated mice. The methods involve both in-vivo re-specification of hepatocytes thereby inducing a degree of beta cell function in mouse liver and in-vitro re-specification of non-insulin expressing cells to an insulin producing phenotype. To explore induced insulin producing cells in mouse liver, we have employed viral delivery of the three beta cell transcription factors. To maximize the chances of all three genes being delivered simultaneously we have made constructs containing the three transcription factors linked by the 2A sequences. This three-gene cassette has been introduced into adenovirus vectors. The adenoviral constructs have been used both for in-vivo expression in mouse hepatocytes and in-vitro in rat pancreatic exocrine cells. In both systems the reagents produce a high yield of cells with high insulin content. Efficiency has been evaluated by gene, expression, insulin production and secretion and the ability of the re-specified cells to maintain glucose homeostasis in diabetic mice.