title: Raising HDL with CETP inhibitor torcetrapib improves glucose homeostasis in dyslipidemic and insulin resistant hamsters.
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.
authors: Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France. Electronic address: f.briand@physiogenex.com.
authors: François
authors: F
authors: Briand
authors: Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors: Bénédicte
authors: B
authors: Prunet-Marcassus
authors: Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors: Quentin
authors: Q
authors: Thieblemont
authors: Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors: Clément
authors: C
authors: Costard
authors: Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors: Elodie
authors: E
authors: Muzotte
authors: Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors: Sylvie
authors: S
authors: Sordello
authors: Physiogenex SAS, Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France.
authors: Thierry
authors: T
authors: Sulpice
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood*; D006224:Cricetinae; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004789:Enzyme Activation / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006943:Hyperglycemia / Q000517:prevention & control; D007333:Insulin Resistance; D008297:Male; D008647:Mesocricetus; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013045:Species Specificity
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D011804:Quinolines; C483909:torcetrapib; D003847:Deoxyglucose; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Cholesteryl ester transfer protein inhibition; Glucose metabolism; High density lipoprotein; Insulin resistance; Reverse cholesterol transport