Received for publication March 14, 2007.
Revised July 16, 2007.
Accepted for publication July 16, 2007.

Simvastatin protects against multiple low dose streptozotocin induced type 1 diabetes in CD-1 mice and recurrence of disease in non obese diabetic mice

Abstract

Statins are drugs well-known for their cholesterol lowering properties. Lately statins have been shown to possess anti-inflammatory properties, which might be attributed to inhibition of leukocyte adhesion and migration to sites of inflammation. We have therefore explored the effects of administration of simvastatin (30 mg/kg body weight given intraperitoneally once a day, from day 4-14) on the development of diabetes induced by multiple low dose streptozotocin (MLDS) in CD-1 mice, a Type 1 diabetes model. We found that treatment with simvastatin could delay and in certain mice fully protect against MLDS induced diabetes. The protective effect could last up to 3 weeks after simvastatin treatment was ended. Morphological examinations of the pancreas suggest that simvastatin might reduce the islet inflammation. Based on experiments in vitro, using isolated pancreatic islets, we conclude that the protective effect of simvastatin is not mediated by a direct effect on streptozotocin action, but rather the result of an immunomodulatory effect. This was reinforced by the finding that simvastatin treatment also prolonged islet function in the recurrence of disease model in diabetic non obese diabetic mice.

Key words: CD-1 mice, beta-cells, pancreatic islets, simvastatin, streptozotocin, type 1 diabetes