The protective effect of simvastatin against low dose streptozotocin induced type 1 diabetes in mice is independent of inhibition of HMG-CoA reductase

Biochemical and Biophysical Research Communications
Tobias Rydgren, Stellan Sandler

Abstract

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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Jul 20, 2007·The Journal of Pharmacology and Experimental Therapeutics·Tobias RydgrenStellan Sandler

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Citations

Sep 29, 2011·World Journal of Diabetes·David J Hill
Jan 24, 2014·Advances in Pharmacological Sciences·F O OmoruyiA O Okorodudu
Oct 1, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Vinayagam RamachandranPoomalai Senthilraja
Jan 13, 2011·The American Journal of Pathology·Arturo Bravo-NuevoLaura E Benjamin
Nov 1, 2012·European Journal of Pharmacology·Rajendran Naresh KumarPanchanatham Sachdanandam
Apr 15, 2010·American Journal of Physiology. Endocrinology and Metabolism·K C MarchandD J Hill

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