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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on July 17, 2007; DOI: 10.1124/jpet.107.122655

0022-3565/07/3231-180-185$20.00
JPET 323:180-185, 2007
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ENDOCRINE AND DIABETES

Simvastatin Protects against Multiple Low-Dose Streptozotocin-Induced Type 1 Diabetes in CD-1 Mice and Recurrence of Disease in Nonobese Diabetic Mice

Tobias Rydgren, Outi Vaarala, and Stellan Sandler

Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden (T.R., S.S.); and Department of Molecular and Clinical Medicine, Linköping University, Linköping, Sweden (O.V.)

Statins are drugs well known for their cholesterol-lowering properties. Lately, statins have been shown to possess anti-inflammatory properties that might be attributed to inhibition of leukocyte adhesion and migration to sites of inflammation. Therefore, we have explored the effects of administration of simvastatin (30 mg/kg body weight given i.p. once a day, from days 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 nonobese diabetic mice.

Received March 13, 2007; accepted July 16, 2007.

Address correspondence to: Tobias Rydgren, Department of Medical Cell Biology, Biomedicum, P.O. Box 571, SE-75123 Uppsala, Sweden. E-mail: Tobias.Rydgren{at}mcb.uu.se






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