Morphological changes in the rat endocrine pancreas within 12 h of intravenous streptozotocin administration

We examined early morphological changes in pancreatic endocrine cells within 12 h of intravenous streptozotocin (STZ) administration (60 mg/kg). Thirty rats were allocated either to a control group (vehicle alone) or to one of four experimental groups tested after 3, 6, 9 and 12 h. Karyopyknosis and cytoplasmic vacuoles were first observed in beta-cell cytoplasm 3 h after STZ administration (STZ-3 h), and the most severe damage was found in beta cells at STZ-12 h. Insulin-positive non-islet cells were observed near the intercalated duct (ICD) and/or centroacinar (CA) cells at STZ-6 h and their numbers peaked at STZ-6 h. The distribution patterns of the insulin-positive cells and those of nestin and insulin-like growth factor-1 were similar and their nuclei were positive for proliferating cell nuclear antigen. Thus, ICD cells and/or CA cells reacted immediately to transform into insulin-secreting cells to replace injured beta cells (or to compensate for the lack of beta cells) within 12 h of STZ administration.