ObjectiveThe purpose of this study was to investigate the mechanisms and characteristics of hyperglycemia-induced liver injury in streptozotocin-induced juvenile diabetic cynomolgus monkeys with poor glycemic control. MethodsA total of eight cynomolgus monkeys (3 years old) were used in this experiment. Four monkeys were induced insulin-dependent diabetes mellitus for four years. Other four age-matched healthy monkeys were used as the controls. Blood tests, periodic acid-Schiff (PAS) staining, Sudan III staining, Gordon-Sweet staining, Masson trichrome staining, conventional light microscopic and ultrastructural morphometry of the liver tissue were performed in both groups. ResultsTotal bile acid, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, cholinesterase, lactate dehydrogenase, total cholesterol, triglyceride and low density lipoprotein cholesterol levels were significantly increased in the diabetic monkeys than in the normal monkeys. Histological examination showed swollen hepatocytes, increased number of positive PAS staining and Sudan III staining cells. Ultrastructural observation indicated that hepatocytes contained a drastic increase of glycogen granules and high electron-dense mitochondria, and hepatic stellate cells were also considerably more numerous in the diabetic livers. ConclusionsJuvenile diabetic cynomolgus monkeys with poorly controlled blood sugar showed specific pathologic changes including excess accumulation of glycogen in hepatocytes and increased number of hepatic stellate cells. These pathologic changes were distinct from nonalcoholic fatty liver disease, however, the mechanisms are unclear yet.