Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion

Andrew L. Siebel, Alaina K Natoli, Felicia Y T Yap, Andrew L. Carey, Medini Reddy-Luthmoodoo, Dmitri Sviridov, Chek Ing Kiu Weber, Georgina Meneses-Lorente, Cyrille Maugeais, Josephine M. Forbes, Bronwyn A. Kingwell

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RATIONALE:: 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. METHODS AND 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.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalCirculation Research
Issue number2
Publication statusPublished - 5 Jul 2013
Externally publishedYes


  • cholesterol homeostasis
  • high-density lipoprotein cholesterol
  • insulin secretion
  • lipoproteins
  • oxidized low-density lipoprotein
  • type 2 diabetes mellitus

Cite this

Siebel, A. L., Natoli, A. K., Yap, F. Y. T., Carey, A. L., Reddy-Luthmoodoo, M., Sviridov, D., Weber, C. I. K., Meneses-Lorente, G., Maugeais, C., Forbes, J. M., & Kingwell, B. A. (2013). Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion. Circulation Research, 113(2), 167-175. https://doi.org/10.1161/CIRCRESAHA.113.300689