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Prescription Diabetes Drugs
Posted by admin in Prescription Diabetes Drugs on May 09th, 2011
Researchers reveal a novel pleiotropic effect for atorvastatin in patients with Type 2 diabetes, demonstrating an increase in circulating levels of a splice variant of the soluble form of the receptor for advanced glycation end-products (esRAGE).
The RAGE plays an important role in the pathogenesis of diabetic complications and atherosclerosis, note Kathryn Tan (University of Hong Kong) and colleagues.
They explain: “Interfering with the activation of RAGE by using a soluble form of the receptor (sRAGE) ameliorates the vascular complications of diabetes in animal models.”
sRAGE levels are modulated by some currently available pharmacological agents including atorvastatin. Tan and her team investigated the effect of the statin on the expression of sRAGE and esRAGE.
The researchers incubated human monocytic leukemia cells (THP-1) with atorvastatin for 24 hours. Levels of sRAGE and esRAGE in the medium were measured by Western immunoblot.
They found that atorvastatin increased the production of both esRAGE and sRAGE by macrophages in vitro.
The effect of atorvastatin on sRAGE in cell culture studies may not directly translate to in vivo settings, the researchers note. They therefore measured serum levels of sRAGE and esRAGE by ELISA at baseline and after 6 months in stored frozen serum samples of Chinese patients with Type 2 diabetes who had participated in a randomized, placebo-controlled trial exploring the cardiovascular effects of atorvastatin.
Atorvastatin significantly increased serum levels of esRAGE, whereas the effect on sRAGE was less marked. There was also a correlation between the increase in serum levels of esRAGE and a reduction in serum low-density lipoprotein cholesterol levels.
The potential benefits of modulating sRAGE for the prevention and treatment of diabetic complications have been demonstrated in animal studies, say the authors.
“Whether modulating sRAGE and/or esRAGE is a potential useful therapeutic approach in human diabetes will have to be evaluated in long-term prospective interventional studies with cardiovascular end-points,” they conclude.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
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