Effects of HDL Elevation with CETP Inhibition on Insulin Secretion

Rationale: High-density lipoprotein (HDL) cholesterol elevation via cholesteryl ester transfer protein (CETP) inhibition represents a novel therapy for atherosclerosis, which may also have relevance for type 2 diabetes. Objective: The current study assessed the effects of a CETP inhibitor (CETPi) on postprandial insulin, ex vivo insulin secretion and cholesterol efflux from pancreatic β-cells. Methods and Results: Healthy participants received a daily dose of CETPi (n=10) or placebo (n=15) for 14 days in a randomized, double-blind study. Insulin secretion and cholesterol efflux from MIN6N8 β-cells was determined following incubation with treated plasma. CETP inhibition increased plasma HDL cholesterol, apoAI and postprandial insulin. MIN6N8 β-cells incubated with plasma from CETPi-treated individuals (vs placebo) exhibited an increase in both glucose-stimulated insulin secretion (GSIS) and cholesterol efflux over the 14 day treatment period. Conclusions: CETP inhibition increased postprandial insulin and promoted ex vivo β-cell GSIS, potentially via enhanced β-cell cholesterol efflux.