| Autor: |
Mittra, S, Sangle, G, Tandon, R, Sharma, S, Roy, S, Khanna, V, Gupta, A, Sattigeri, J, Sharma, L, Priyadarsiny, P, Khattar, S K, Bora, R S, Saini, K S, Bansal, V S |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Feb2007, Vol. 150 Issue 4, p480-487, 8p |
| Abstrakt: |
Background and purpose:Muraglitazar, a dual PPARα/γ agonist, caused a robust increase in body weight in db/db mice. The purpose of the study was to see if this increase in weight was due to oedema and/or adipogenesis.Experimental approach:The affinity of muraglitazar at PPARα/γ receptors was characterized using transactivation assays. Pre-adipocyte differentiation, expression of genes for adipogenesis (aP2), fatty acid oxidation (ACO) and sodium reabsorption (ENaCγ and Na+, K+-ATPase); haemodilution parameters and serum electrolytes were measured to delineate the role of muraglitazar in causing weight gain vis a vis rosiglitazone.Key Results:Treatment with muraglitazar (10 mg kg−1) for 14 days significantly reduced plasma glucose and triglycerides. Reduction in plasma glucose was significantly greater than after similar treatment with rosiglitazone (10 mg kg−1). A marked increase in weight was also observed with muraglitazar that was significantly greater than with rosiglitazone. Muraglitazar increased aP2 mRNA and caused adipocyte differentiation in 3T3-L1 cells similar to rosiglitazone. It also caused a marked increase in ACO mRNA in the liver of the treated mice. Expression of mRNA for ENaCγ and Na+, K+-ATPase in kidneys was up-regulated after either treatment. Increased serum electrolytes and decreased RBC count, haemoglobin and haematocrit were observed with both muraglitazar and rosiglitazone.Conclusions and implications:Although muraglitazar has a better glucose lowering profile, it also has a greater potential for weight gain than rosiglitazone. In conclusion, muraglitazar causes both robust adipogenesis and oedema in a 14-day treatment of db/db mice as observed in humans.British Journal of Pharmacology (2007) 150, 480–487. doi:10.1038/sj.bjp.0707000; published online 8 January 2007 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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