Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells.

A decrease in the number of functioning pancreatic beta-cells and insufficient insulin biosynthesis and/or secretion are the hallmarks of diabetes. Therefore, the identification of alternative sources to induce insulin-producing surrogate beta-cells is of great importance. For the induction of insulin-producing cells from various cells and/or tissues, it is useful to mimic and reproduce expression alterations of various pancreatic transcription factors observed during normal pancreas development and to induce key pancreatic transcription factors which have the potency to induce insulin and other beta-cell-related genes. MafA, PDX-1 and NeuroD directly bind to the insulin gene promoter and function as very important transcription factors in pancreatic beta-cell differentiation and mature beta-cell function. The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells.