Expression of transcription factors and precursor cell markers during regeneration of beta cells in pancreata of rats treated with streptozotocin.

An understanding of beta cell regeneration is needed if we are to develop new treatment modalities in diabetes mellitus. Lineage tracing studies have shown that all pancreatic cell types, including beta cells, arise from PDX-1-expressing precursor cells. We studied beta cell regeneration by analyzing the immunocytochemical expression of the transcription factors, PDX-1, PBX-1, and MEIS2, and that of the potential precursor cell markers, c-Kit and nestin, using the model of streptozotocin (STZ)-induced diabetes in rats. The pancreata were examined 3, 7, and 14 days after STZ administration. PDX-1 expression, but not that of MEIS2 and PBX-1, transiently increased on day 7. c-Kit expression was found to be upregulated in islet cells at all points in time, while nestin expression was lacking. Ki-67 labeling was increased in islets on days 3 and 7. These results suggest that temporary upregulation of PDX-1 and prolonged overexpression of c-Kit may play a role during beta cell regeneration.