Raising HDL with CETP inhibitor torcetrapib improves glucose homeostasis in dyslipidemic and insulin resistant hamsters

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• 作者：Franç ; ois Briand ; ^{f.briand@physiogenex.com" class="auth_mail} ; Bé ; né ; dicte Prunet-Marcassus ; Quentin Thieblemont ; Clé ; ment Costard ; Elodie Muzotte ; Sylvie Sordello ; Thierry Sulpice
• 关键词：Cholesteryl ester transfer protein inhibition ; Reverse cholesterol transport ; High density lipoprotein ; Glucose metabolism ; Insulin resistance
• 刊名：Atherosclerosis
• 出版年：April, 2014
• 年：2014
• 卷：233
• 期：2
• 页码：359-362
• 全文大小：578 K

文摘

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聽mg/kg/day (TOR) administered for 10 days significantly increased by 鈭?0% both HDL-cholesterol levels and ³H-tracer appearance in HDL after ³H-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聽<聽0.01). After ³H-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.