Inhibition of immune-mediated low-dose streptozotocin diabetes by agents which reduce vascular permeability.

Low-dose streptozotocin treatment in C57Bl/6J mice causes development of hyperglycemia within two weeks. Diabetes development is due to the specific loss of beta cells from pancreatic islets which can be blocked by immunosuppressive treatment. The role of vascular permeability in pancreatic islet destruction was studied by administration of methysergide or pargyline in addition to low-dose streptozotocin. Both drugs impair serotonin-enhanced vascular permeability. Administration of methysergide or pargyline during the first 11 days following streptozotocin treatment caused substantial suppression of diabetes development. These observations suggest a role of enhanced vascular permeability in immune-mediated beta cell destruction.