Diabetogenic action of streptozotocin: essential role of membrane permeability.

A single high dose of streptozotocin was found to cause a transient increase in islet capillary permeability 2-4 h after administration. Staining of areas of increased vascular permeability by Evans blue showed that islets, but not exocrine tissue, were affected. The permeability increase seems to involve vasoactive substances released by mast cells. A mast cell inhibitor (disodium cromoglycate) and a serotonin antagonist (methysergide) were found protective. Furthermore, administration of methysergide partially prevented the development of hyperglycaemia in streptozotocin-treated rats. In mice, almost full protection from diabetes development was reached by both methysergide and disodium cromoglycate. Our observations indicate an important role of mast cell controlled membrane permeability in this model of beta-cell destruction and diabetes development.