title: Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion.
abstract: BACKGROUND
  High-density lipoprotein cholesterol elevation via cholesteryl ester transfer protein (CETP) inhibition represents a novel therapy for atherosclerosis, which also may have relevance for type 2 diabetes mellitus.
  
  
  OBJECTIVE
  The current study assessed the effects of a CETP inhibitor on postprandial insulin, ex vivo insulin secretion, and cholesterol efflux from pancreatic β-cells.
  
  
  RESULTS
  Healthy participants received a daily dose of CETP inhibitor (n=10) or placebo (n=15) for 14 days in a randomized double-blind study. Insulin secretion and cholesterol efflux from MIN6N8 β-cells were determined after incubation with treated plasma. CETP inhibition increased plasma high-density lipoprotein cholesterol, apolipoprotein AI, and postprandial insulin. MIN6N8 β-cells incubated with plasma from CETP inhibitor-treated individuals (compared with placebo) exhibited an increase in both glucose-stimulated insulin secretion and cholesterol efflux over the 14-day treatment period.
  
  
  CONCLUSIONS
  CETP inhibition increased postprandial insulin and promoted ex vivo β-cell glucose-stimulated insulin secretion, potentially via enhanced β-cell cholesterol efflux.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Siebel
authors.forename: Alaina K
authors.initials: AK
authors.lastname: Natoli
authors.forename: Felicia Y T
authors.initials: FY
authors.lastname: Yap
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Carey
authors.forename: Medini
authors.initials: M
authors.lastname: Reddy-Luthmoodoo
authors.forename: Dmitri
authors.initials: D
authors.lastname: Sviridov
authors.forename: Chek Ing Kiu
authors.initials: CI
authors.lastname: Weber
authors.forename: Georgina
authors.initials: G
authors.lastname: Meneses-Lorente
authors.forename: Cyrille
authors.initials: C
authors.lastname: Maugeais
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Forbes
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
mesh_terms: D000577:Amides; D000818:Animals; D002460:Cell Line; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D004311:Double-Blind Method; D004952:Esters; D005215:Fasting / Q000097:blood; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000577:Amides; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004952:Esters; D007328:Insulin; D013438:Sulfhydryl Compounds; C411602:dalcetrapib
keywords: cholesterol homeostasis; high-density lipoprotein cholesterol; insulin secretion; lipoproteins; oxidized low-density lipoprotein; type 2 diabetes mellitus