Methods are disclosed for producing pancreatic beta cells in a subject. The methods include administering to the subject a vector encoding heterologous Pancreas duodenal homeobox protein (Pdx) 1 and MafA, wherein the vector does not encode Neurogenin 3 (Ngn3) and wherein the subject is not administered any other nucleic acid encoding Ngn3. The vector is administered intraductally into a pancreatic duct of the subject. Compositions are disclosed that include a) a viral vector comprising a promoter operably linked to a nucleic acids encoding Pdx1 and a nucleic acid encoding MafA, wherein the vector does not encode Ngn3 b) a buffer and c) a contrast dye for endoscopic retrograde cholangiopancreatography. These compositions are of use in any of the methods disclosed herein.
