Regeneration of Pancreatic Cells from Intra-Islet Precursor Cells in an Experimental Model of Diabetes

Abstract

We previously reported that new cells differentiated in pan- creatic islets of mice in which diabetes was produced by in- jection of a high dose of the cell toxin streptozotocin (SZ), which produces hyperglycemia due to rapid and massive cell death. After SZ-mediated elimination of existing cells, a population of insulin containing cells reappeared in islets. However, the number of new cells was small, and the animals remained severely hyperglycemic. In the present study, we tested whether restoration of normoglycemia by exogenous administered insulin would enhance cell differentiation and maturation. We found that cell regeneration improved in SZ-treated mice animals that rapidly attained normoglycemia following insulin administration because the number of cells per islet reached near 40% of control values during the first week after restoration of normoglycemia. Two presump- tive precursor cell types appeared in regenerating islets. One expressed the glucose transporter-2 (Glut-2), and the other cell type coexpressed insulin and somatostatin. These cells probably generated the monospecific cells containing insulin that repopulated the islets. We conclude that cell neogenesis occurred in adult islets and that the outcome of this process was regulated by the insulin-mediated normalization of cir- culating blood glucose levels. (Endocrinology 142: 4956 - 4968, 2001)