title: Simvastatin protects against multiple low-dose streptozotocin-induced type 1 diabetes in CD-1 mice and recurrence of disease in nonobese diabetic mice.
abstract: 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.
authors.affiliation: Department of Medical Cell Biology, Biomedicum, P.O. Box 571, SE-75123 Uppsala, Sweden. Tobias.Rydgren@mcb.uu.se
authors.forename: Tobias
authors.initials: T
authors.lastname: Rydgren
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Stellan
authors.initials: S
authors.lastname: Sandler
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D055502:Secondary Prevention; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D013311:Streptozocin; D019821:Simvastatin; D005947:Glucose