Streptozotocin and Insulin-Dependent Diabetes Induce Changes in Hepatic Cytoarchitecture in Mice

Streptozotocin (STZ) causes both direct organ toxicity and diabetes, and both actions can affect the structure and function of many organs. Because biliary excretory function changes with time after STZ injection, it was hypothesized that morphological changes would occur in livers from mice made diabetic with STZ. Blood glucose concentrations were elevated above that in control mice from day 3 onward. Liver tissue collected on days 1, 3, 5, 7, 14, 21, 28, 35, and 42 following a single administration of STZ (200 mg/kg IV) was prepared for electron microscopy using standard procedures. Liver samples from vehicle control mice were obtained on each experimental day for comparison. Morphological changes on days 1 and 3 included a swelling of the hepatic sinusoids, an apparent widening between hepatocyte borders, and deterioration of the microvilli of the bile canaliculi. On days 5, 7, 14, 21, and 28, the liver exhibited normal extracellular space and canaliculi with regenerated microvilli. However, findings similar to those from days 1 and 3 were observed in the liver samples from days 35 and 42. The most dramatic effect seen on day 42 was the dilation of extracellular space. Hepatic sinusoids were enlarged and canalicular microvilli appeared to have degenerated. Findings from days 1 and 3 may be attributed to STZ hepatotoxicity with subsequent normalization of the fiver, whereas the alterations observed on days 35 and 42 are probably a manifestation of diabetes mellitus, because these changes became more extensive with progression of the disease.