The influence of cyclosporin A on the vascular permeability of the pancreatic islets and on diabetes induced by multiple low doses of streptozotocin in the mouse

Abstract

The aim of the present study was to investigate the influence of cyclosporin A on the course of multiple low dose streptozotocin induced diabetes in mice, an animal model for human type I diabetes mellitus. C57BL/Ks mice were treated on five consecutive days with intraperitoneal injections of streptozotocin or citiric acid buffer. Thirty min before the injections the animals were given cyclosporin A (10 or 50 mg/kg body weight) or saline. Cyclosporin A did not protect against the hypoglycaemia and at the higher dose it potentiated the diabetogenic effect. Furthermore, cyclosporin A did not affect the development of insulitis when the pancreatic glands were examined by light microscopy. Using a technique for monitoring vascular permeability in vivo with the aid of the pigment Monastral Blue B, it was found that the development of diabetes was accompanied by an increased vascular leakage. Control animals treated with cyclosporin A also showed an increased islet staining with Monastral Blue B. The data indicate that cyclosporin A potentiates diabetes induced by low doses of streptozotocin. This can be attributed to a direct toxic effect of cyclosporin A on the pancreatic B-cells and may also be due to an increased vascular leakage induced by cyclosporin A. The latter would allow an increased migration of inflammatory cells into the islets and the consequent release of B-cytotoxic substances.