. . "0"^^ . "Dose-dependent involvement of the adiponectin-AMPK axis in insulin-sensitizing effects of thizolidinediones"@en . "rosiglitazone adiponektin liver muscle adipose tissue sub-optimal dose"@en . . "2014-03-31+02:00"^^ . "2011-01-01+01:00"^^ . . "GAP301/11/0226" . . . "1"^^ . . "1"^^ . . "Thiazolidinediones (TZDs) are used for the treatment of insulin resistance in diabetic patients; however, the therapy is associated with unwanted side effects. Novel treatment strategies are required allowing for the use of sub-optimal doses of TZDs in combination with other pharmacological or dietary interventions. The insulin-sensitizing effect of TZDs is thought to results from activation of PPAR\u03B3, associated with the induction of adiponectin and stimulation of AMP-activated protein kinase (AMPK). However, our data suggest that the mechanism underlying effects of sub-optimal doses of TZDs on insulin sensitivity may depend on a change of plasma lipid profile resulting from modulation of hepatic lipid metabolism by TZDs, independent of the adiponectin-AMPK axes. The goal of this project is to characterize the dose-dependent mechanism of TZDs action using mice with genetically disrupted AMPK. Characterization of the mechanisms behind the dose-dependent effects TZDs will allow for designing novel combination treatment strategies, while reducing both the risks an the cost of the TZD therapy."@en . . "5"^^ . . "5"^^ . . . . "http://www.isvav.cz/projectDetail.do?rowId=GAP301/11/0226"^^ . "Thiazolidinediony (TZD) jsou \u0161iroce pou\u017E\u00EDv\u00E1ny p\u0159i l\u00E9\u010Db\u011B inzulinov\u00E9 resistence u diabetik\u016F. Tato l\u00E9\u010Dba je v\u0161ak spojena s\u00A0n\u011Bkter\u00FDmi ne\u017E\u00E1douc\u00EDmi \u00FA\u010Dinky. Je proto zapot\u0159eb\u00ED nov\u00FDch l\u00E9\u010Debn\u00FDch postup\u016F, kter\u00E9 by umo\u017Enily pou\u017E\u00EDt ni\u017E\u0161\u00EDch (suboptim\u00E1ln\u00EDch) d\u00E1vek \u00A0TZD v kombinaci s\u00A0dal\u0161\u00EDmi farmakologick\u00FDmi \u010Di dietetick\u00FDmi intervencemi. \u00DA\u010Dinek TZD na inzulinovou citlivost je vysv\u011Btlov\u00E1n aktivac\u00ED PPAR\u03B3 nukle\u00E1rn\u00EDch receptor\u016F, kter\u00E1 je spojena se\u00A0zv\u00FD\u0161enou produkc\u00ED adiponektinu a stimulac\u00ED AMP aktivovan\u00E9 proteinov\u00E9 kin\u00E1zy (AMPK). Na\u0161e v\u00FDsledky v\u0161ak nazna\u010Duj\u00ED, \u017Ee\u00A0 mechanizmus \u00FA\u010Dinku suboptim\u00E1ln\u00EDch d\u00E1vek TZD je pravd\u011Bpodobn\u011B nez\u00E1visl\u00FD na ose adiponektin-AMPK a odr\u00E1\u017E\u00ED modulaci jatern\u00EDho lipidov\u00E9ho metabolismu vlivem TZD, co\u017E vede ke zm\u011Bn\u00E1m lipidov\u00E9ho profilu v plazm\u011B. C\u00EDlem tohoto\u00A0 projektu je analyzovat \u00FA\u010Dinek TZD na modelu my\u0161i s\u00A0vy\u0159azen\u00FDm genem pro AMPK, v\u00A0z\u00E1vislosti na jejich d\u00E1vce. Odhalen\u00ED mechanismu \u00FA\u010Dinku r\u016Fzn\u00FDch d\u00E1vek TZD pom\u016F\u017Ee navrhnout nov\u00E9 postupy kombinovan\u00E9 l\u00E9\u010Dby, kter\u00E9 omez\u00ED mo\u017En\u00E1 rizika l\u00E9\u010Dby a sn\u00ED\u017E\u00ED tak\u00E9 jej\u00ED finan\u010Dn\u00ED n\u00E1ro\u010Dnost." . "2015-04-23+02:00"^^ . "2015-12-31+01:00"^^ . . . "V\u00FDznam osy adiponektin-AMPK pro \u00FA\u010Dinek thiazolidindion\u016F na inzulinovou citlivost v z\u00E1vislosti na jejich d\u00E1vce" . . . .