Generation of insulin-secreting cells from pancreatic acinar cells of animal models of type 1 diabetes

1 Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto; 2 Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe; and 3 Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan Submitted 13 April 2006 ; accepted in final form 21 August 2006 We recently found that pancreatic acinar cells isolated from normal adult mouse can transdifferentiate into insulin-secreting cells in vitro. Using two different animal models of type 1 diabetes, we show here that insulin-secreting cells can also be generated from pancreatic acinar cells of rodents in the diabetic state with absolute insulin deficiency. When pancreatic acinar cells of streptozotocin-treated mice were cultured in suspension in the presence of epidermal growth factor and nicotinamide under low-serum condition, expressions of insulin genes gradually increased. In addition, expressions of other pancreatic hormones, including glucagon, somatostatin, and pancreatic polypeptide, were also induced. Analysis by the Cre/loxP-based direct cell lineage tracing system revealed that these newly made cells originated from amylase-expressing pancreatic acinar cells. Insulin secretion from the newly made cells was significantly stimulated by high glucose and other secretagogues. In addition, insulin-secreting cells were generated from pancreatic acinar cells of Komeda diabetes-prone rats, another animal model of type 1 diabetes. The present study demonstrates that insulin-secreting cells can be generated by transdifferentiation from pancreatic acinar cells of rodents in the diabetic state and further suggests that pancreatic acinar cells represent a potential source of autologous transplantable insulin-secreting cells for treatment of type 1 diabetes. transdifferentiation; lineage tracing; streptozotocin; Komeda diabetes-prone rat Address for reprint requests and other correspondence: S. Seino, Division of Cellular and Molecular Medicine, Kobe Univ. Graduate School of Medicine, Kobe 650-0017, Japan (e-mail: seino{at}med.kobe-u.ac.jp )