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Raising HDL with CETP inhibitor torcetrapib improves glucose homeostasis in dyslipidemic and insulin resistant hamsters.
- Source :
-
Atherosclerosis [Atherosclerosis] 2014 Apr; Vol. 233 (2), pp. 359-362. Date of Electronic Publication: 2014 Jan 23. - Publication Year :
- 2014
-
Abstract
- 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 ∼40% 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<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.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- AMP-Activated Protein Kinases drug effects
Animals
Anticholesteremic Agents pharmacology
Apolipoprotein A-I blood
Apolipoproteins E blood
Cricetinae
Deoxyglucose pharmacokinetics
Diet, Atherogenic
Disease Models, Animal
Drug Evaluation, Preclinical
Dyslipidemias blood
Dyslipidemias etiology
Enzyme Activation drug effects
Feces chemistry
Homeostasis drug effects
Hyperglycemia prevention & control
Male
Mesocricetus
Muscle, Skeletal drug effects
Muscle, Skeletal metabolism
Quinolines pharmacology
Random Allocation
Species Specificity
Anticholesteremic Agents therapeutic use
Cholesterol Ester Transfer Proteins antagonists & inhibitors
Cholesterol, HDL blood
Dyslipidemias drug therapy
Glucose metabolism
Insulin Resistance
Quinolines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1484
- Volume :
- 233
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 24530763
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2014.01.028