DYNAMICS OF PANCREATIC-CELL GROWTH AND DIFFERENTIATION DURING DIABETES REVERSION IN STZ-TREATED NEWBORN RATS

Cellular processes underlying ontogenesis and regression of streptozot ocin (STZ)induced diabetes in newborn rats were investigated at the mo st severe stage of diabetes at day 3 and after recovery of normoglycem ia at day 8 by immunocytochemistry and quantitative analysis. A previo usly unknown endocrine cell type subpopulation (PEPS) was identified. It was characterized by granule polymorphism, coexpression of insulin and glucagon immunoreactivity, and a proliferative capacity transientl y higher than in B cells. In STZ-treated rats at day 3, B cell mass de creased 14-fold, whereas PEPS cells were unaffected. The islet mass wa s restored to 55.7% by day 8, with a concomitant appearance of numerou s small islets contiguous to small ducts. B cell mass increased by 6.9 -fold compared with 1.8-fold in control rats, although proliferative c apacities remained similar. Proliferation dropped considerably by day 8, preventing complete B cell mass recovery in STZ-treated rats. STZ-i nduced 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.