Document Detail


The protective effect of simvastatin against low dose streptozotocin induced type 1 diabetes in mice is independent of inhibition of HMG-CoA reductase.
MedLine Citation:
PMID:  19150339     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Tobias Rydgren; Stellan Sandler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-14
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  379     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-03-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1076-9     Citation Subset:  IM    
Affiliation:
Department of Medical Cell Biology, Uppsala University, Husargatan 3, P.O. Box 571, Biomedicum, SE-75123 Uppsala, Sweden. Tobias.Rydgren@mcb.uu.se
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MeSH Terms
Descriptor/Qualifier:
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:
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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