CB1R antagonist increases hepatic insulin clearance in fat-fed dogs likely via upregulation of liver adiponectin receptors.
作者： Morvarid Kabir , Malini S. Iyer , Joyce M. Richey , Orison O. Woolcott , Isaac Asare Bediako
DOI: 10.1152/AJPENDO.00196.2015
关键词:
摘要: The improvement of hepatic insulin sensitivity by the cannabinoid receptor 1 (CB1R) antagonist rimonabant (RIM) has been recently reported to be due upregulation adiponectin. Several studies demonstrated that in clearance accompanies enhancement sensitivity. However, effects RIM on (HIC) have not fully explored. aim this study was explore molecular mechanism(s) which affects HIC, specifically determine whether liver adiponectin receptors (ADRs) and other key genes regulated mediate effects. To induce resistance skeletal muscle liver, dogs were fed a hypercaloric high-fat diet (HFD) for 6 wk. Thereafter, while still maintained HFD, animals received (HFD+RIM; n = 11) or placebo (HFD+PL; 9) an additional 16 calculated as metabolic rate (MCR), estimated from euglycemic-hyperinsulinemic clamp. HFD+PL group showed decrease MCR; contrast, HFD+RIM increased MCR. Consistently, expression involved CEACAM-1 IDE, well gene ADRs, group, but group. We also found positive correlation between insulin-degrading enzyme IDE with ADRs. Interestingly, lipid oxidation conclude fat-fed enhances appears linked pathway.
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