| The protective effect of simvastatin against low dose streptozotocin induced type 1 diabetes in mice is independent of inhibition of HMG-CoA reductase. | |
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MedLine Citation:
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PMID: 19150339 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tobias Rydgren; Stellan Sandler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-14 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 379 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-06 Completed Date: 2009-03-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 1076-9 Citation Subset: IM |
Affiliation:
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Department of Medical Cell Biology, Uppsala University, Husargatan 3, P.O. Box 571, Biomedicum, SE-75123 Uppsala, Sweden. Tobias.Rydgren@mcb.uu.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Diabetes Mellitus, Experimental / prevention & control* Diabetes Mellitus, Type 1 / prevention & control* Hydroxymethylglutaryl CoA Reductases / metabolism Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* Lymphocyte Function-Associated Antigen-1 / metabolism Male Mice Mice, Inbred Strains Simvastatin / pharmacology* Streptozocin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Lymphocyte Function-Associated Antigen-1; 18883-66-4/Streptozocin; 79902-63-9/Simvastatin; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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