Mechanisms of Toxic Effect of Streptozotocin on beta-cells in the Islets of Langerhans

摘要

Administration of streptozotocin caused selective damage to endocrine beta-cells in rat pancreatic islets, which was related to activation of apoptosis. The cytotoxic effect of streptozotocin was associated not only with DMA damage due to dysfunction of the antioxidant defense system, but also with activation of the caspase cascade and TNF-related apoptosis-inducing ligand.Diabetes mellitus (DM) is a global medicosocial problem in various countries all over the world. The disease is associated with early disability and death resulting from the development of late complications [1].Selective beta-cytotoxins, including alloxan, uric acid derivatives, and streptozotocin (STZ), are extensively used to produce DM in animals [11]. These substances are not characterized by individual variability of beta-cytotoxicity, because they cause damage to beta-cells in all animals of various species. Administration of STZ suppresses DNA synthesis and cell proliferation, inhibits mitosis, and activates apoptosis [12]. However, specific mechanisms for STZ-induced apoptosis are poorly understood.