Raising HDL with CETP inhibitor torcetrapib improves glucose homeostasis in dyslipidemic and insulin resistant hamsters
Raising HDL with CETP inhibitor torcetrapib improves glucose homeostasis in dyslipidemic and insulin resistant hamsters
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DOI：
10.1016/j.atherosclerosis.2014.01.028
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发表时间：
2014-04-01
期刊：
影响因子：
5.3
通讯作者：
Sulpice, Thierry
中科院分区：
文献类型：
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作者：
Briand, Francois;Prunet-Marcassus, Benedicte;Sulpice, Thierry
我们研究了胆固醇酯转移蛋白（CETP）抑制剂是否能提高HDL-胆固醇水平，改善血脂异常和胰岛素抵抗仓鼠的葡萄糖稳态。与媒介物相比，在腹膜内注射H-3-胆固醇标记的巨噬细胞后，施用10天的托塞曲匹30 mg/kg/天（TOR）显著增加HDL-胆固醇水平和HDL中的H-3-示踪物出现，增加了类似于40% JOR显著降低空腹血浆甘油三酯、甘油和游离脂肪酸水平，分别降低了65%、31%和23%。TOR还使血糖水平和血浆胰岛素分别降低20%和49%，这导致HOMA-IR指数降低60%（均p < 0.01）。在H-3-2-脱氧葡萄糖和胰岛素注射后，TOR显著增加了氧化比目鱼肌、肝脏和心脏中的葡萄糖摄取，分别增加了26、33和70%。应研究其他CETP抑制剂是否会观察到类似的效果。(C)2014爱思唯尔爱尔兰有限公司版权所有。
We investigated whether raising HDL-cholesterol levels with cholesteryl ester transfer protein (CETP) inhibition improves glucose homeostasis in dyslipidemic and insulin resistant hamsters. Compared with vehicle, torcetrapib 30 mg/kg/day (TOR) administered for 10 days significantly increased by similar to 40% both HDL-cholesterol levels and H-3-tracer appearance in HDL after H-3-cholesterol labeled macrophages i.p. injection.TOR significantly reduced fasting plasma triglycerides, glycerol and free fatty acids levels by 65%, 31% and 23%, respectively. TOR also reduced blood glucose levels and plasma insulin by 20% and 49% respectively, which led to a 60% reduction in HOMA-IR index (all p < 0.01). After H-3-2-deoxyglucose and insulin injection, TOR significantly increased glucose uptake in oxidative soleus muscle, liver and heart by 26, 33 and 70%, respectively.Raising HDL levels with the CETP inhibitor torcetrapib improves glucose homeostasis in dyslipidemic and insulin resistant hamsters. Whether similar effect would be observed with other CETP inhibitors should be investigated. (C) 2014 Elsevier Ireland Ltd. All rights reserved.