HDL biology
CETP expression does not alter glucose tolerance, insulin secretion, or tissue glucose uptake in transgenic mice across multiple conditions (Lipids Health Dis 2016)
Original title: Cholesteryl Ester Transfer Protein (CETP) expression does not affect glucose homeostasis and insulin secretion: studies in human CETP transgenic mice
Testing whether CETP modifies glucose metabolism, as prior studies in patients and cultured cells had suggested, researchers compared human CETP-transgenic mice against non-transgenic littermates on chow or high-fat diets, in adult and aged animals, and in normo- and dyslipidemic backgrounds. CETP expression did not alter glucose or insulin tolerance in any tested condition, and fasting and fed plasma insulin levels did not differ between groups. Direct measurement of isolated pancreatic islet insulin secretion at multiple glucose, KCl, and leucine concentrations showed no difference between CETP and control mice, and in vivo glucose uptake measured with radiolabeled 2-deoxyglucose was unchanged across liver, muscle, and multiple adipose tissue depots, with GLUT1/GLUT4 mRNA levels also unaffected, together indicating CETP expression itself does not impair glucose homeostasis.
Original abstract
Background: Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates the exchange of triglycerides for esterified cholesterol between HDL and apoB-lipoproteins. Previous studies suggest that CETP may modify glucose metabolism in patients or cultured cells. In this study, we tested if stable CETP expression would impair glucose metabolism.
Methods: We used human CETP transgenic mice and non-transgenic littermate controls (NTg), fed with control or high fat diet, as well as in dyslipidemic background and aging conditions. Assays included glucose and insulin tolerance tests, isolated islets insulin secretion, tissue glucose uptake and adipose tissue GLUT mRNA expression.
Results: CETP expression did not modify glucose or insulin tolerance in all tested conditions such as chow and high fat diet, adult and aged mice, normo and dyslipidemic backgrounds. Fasting and fed state plasma levels of insulin were not differ in CETP and NTg mice. Direct measurements of isolated pancreatic islet insulin secretion rates induced by glucose (11, 16.7 or 22 mM), KCl (40 mM), and leucine (10 mM) were similar in NTg and CETP mice, indicating that CETP expression did not affect β-cell function in vivo and ex vivo. Glucose uptake by insulin target tissues, measured in vivo using (3)H-2-deoxyglucose, showed that CETP expression had no effect on the glucose uptake in liver, muscle, perigonadal, perirenal, subcutaneous and brown adipose tissues. Accordingly, GLUT1 and GLUT4 mRNA in adipose tissue were not affected by CETP.
Conclusions: In summary, by comparing the in vivo all-or-nothing CETP expressing mouse models, we demonstrated that CETP per se has no impact on the glucose tolerance and tissue uptake, global insulin sensitivity and beta cell insulin secretion rates.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.