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The protective effect of simvastatin against low dose streptozotocin induced type 1 diabetes in mice is independent of inhibition of HMG-CoA reductase
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 379, no 4, 1076-1079 p.Article in journal (Refereed) Published
Abstract [en]

Besides a cholesterol-lowering effect, simvastatin possesses anti-inflammatory properties attributed to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and/or direct binding to, and inhibition of, the integrin lymphocyte function associated antigen-1 (LFA-1). We have shown that simvastatin protects against multiple low dose streptozotocin (MLDS) induced type 1 diabetes in mice. Presently, we examined if this effect could be abolished by co-administration of mevalonic acid, thus determining if the protective effect is dependent or independent of inhibition of HMG-CoA reductase. Mevalonic acid did not affect the protective effect of simvastatin against MLDS diabetes. Moreover, spleens from these mice did not show any signs of toxic side-effects, thus excluding the possibility that the protective effect is secondary to a general inflammatory response. We suggest that simvastatin's protective effect mainly is independent of HMG-CoA reductase inhibition. This implies that inhibition of LFA-1 activation is important for the protective effect exerted by simvastatin.

Place, publisher, year, edition, pages
2009. Vol. 379, no 4, 1076-1079 p.
Keyword [en]
Simvastatin, Type 1 diabetes, Mevalonic acid, CD-1 mice, HMG-CoA reductase, Lymphocyte function associated antigen-1, Streptozotocin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-98434DOI: 10.1016/j.bbrc.2009.01.017ISI: 000263336700053PubMedID: 19150339OAI: oai:DiVA.org:uu-98434DiVA: diva2:174522
Available from: 2009-02-23 Created: 2009-02-23 Last updated: 2017-12-13Bibliographically approved

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