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

Siebel, Andrew L., Natoli, Alaina K., Yap, Felicia Y. T., Carey, Andrew L., Reddy-Luthmoodoo, Medini, Sviridov, Dmitri, Weber, Chek Ing Kiu, Meneses-Lorente, Georgina, Maugeais, Cyrille, Forbes, Josephine M. and Kingwell, Bronwyn A. (2013) Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion. Circulation Research, 113 2: 167-175. doi:10.1161/CIRCRESAHA.113.300689

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Author Siebel, Andrew L.
Natoli, Alaina K.
Yap, Felicia Y. T.
Carey, Andrew L.
Reddy-Luthmoodoo, Medini
Sviridov, Dmitri
Weber, Chek Ing Kiu
Meneses-Lorente, Georgina
Maugeais, Cyrille
Forbes, Josephine M.
Kingwell, Bronwyn A.
Title Effects of high-density lipoprotein elevation with cholesteryl ester transfer protein inhibition on insulin secretion
Journal name Circulation Research   Check publisher's open access policy
ISSN 0009-7330
1524-4571
Publication date 2013-07-05
Year available 2013
Sub-type Article (original research)
DOI 10.1161/CIRCRESAHA.113.300689
Open Access Status Not Open Access
Volume 113
Issue 2
Start page 167
End page 175
Total pages 9
Place of publication Philadelphia, PA United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
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.
Keyword Cholesterol homeostasis
High-density lipoprotein cholesterol
Insulin secretion
Lipoproteins
Oxidized low-density lipoprotein
Type 2 diabetes mellitus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Health Services Publications
 
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Created: Mon, 15 Dec 2014, 11:48:25 EST by Ms Kate Rowe on behalf of Mater Research Institute-UQ