Dynamics of pancreatic cell growth and differentiation during diabetes reversion in STZ-treated newborn rats

Cellular processes underlying ontogenesis and regression of streptozotocin (STZ)-induced diabetes in newborn rats were investigated at the most severe stage of diabetes at day 3 and after recovery of normoglycemia at day 8 by immunocytochemistry and quantitative analysis. A previously unknown endocrine cell type subpopulation (PEPS) was identified. It was characterized by granule polymorphism, coexpression of insulin and glucagon immunoreactivity, and a proliferative capacity transiently higher than in B cells. In STZ-treated rats at day 3, B cell mass decreased 14-fold, whereas PEPS cells were unaffected. The islet mass was restored to 55.7% by day 8, with a concomitant appearance of numerous small islets contiguous to small ducts. B cell mass increased by 6.9-fold compared with 1.8-fold in control rats, although proliferative capacities remained similar. Proliferation dropped considerably by day 8, preventing complete B cell mass recovery in STZ-treated rats. STZ-induced neonatal diabetes thus stimulates neogenesis of islets close to ducts and proliferation of PEPS cells. Those partially differentiated islet cells appear to be on the differentiation pathway of stem cells to fully differentiated B cells.