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Journal of Lipid Research, Vol. 44, 1870-1876, October 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Cholesteryl ester transfer protein expression is down-regulated in hyperinsulinemic transgenic mice

J. A. Berti, A. C. Casquero, P. R. Patrício, E. J. B. Bighetti, E. M. Carneiro, A. C. Boschero and H. C. F. Oliveira¹

Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, SP, Brazil

¹ To whom correspondence should be addressed. e-mail: ho98{at}unicamp.br

Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester (CE) and triglyceride redistribution among plasma lipoproteins. In this work, we investigated whether varying levels of insulin regulate the CETP expression in vivo. Insulin deficiency [streptozotocin (STZ) injection], and hyperinsulinemia (insulin injections, 14 days) were induced in transgenic mice expressing a human CETP minigene flanked by its natural regulatory sequences. Glucose supplementation was provided to the hyperinsulinemic group (INS+GLUC) and to an extra group of mice (GLUC). In the STZ group, endogenous CE transfer rate, plasma CETP, and hepatic CETP mRNA levels were enhanced 3.0-, 1.5-, and 2.5-fold, respectively, as compared with controls. Insulin replacement in STZ mice normalized their glycemia and liver mRNA levels. Higher plasma CETP levels were observed in GLUC mice, which were decreased in INS+GLUC mice. Hepatic CETP mRNA was not altered in GLUC mice and was reduced by one-third in INS+GLUC mice.

These results show that: 1) STZ treatment increases CETP plasma levels and liver mRNA expression; 2) diet glucose supplementation increases plasma CETP levels but does not change liver mRNA abundance; and 3) daily insulin injections blunt the glucose-stimulated CETP expression by reducing its liver mRNA levels. These data suggest that insulin down-regulates CETP gene expression.

Abbreviations: CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; FPLC, fast-protein liquid chromatography; GLUC, glucose; HL, hepatic lipase; INS, insulin; LP, lipoprotein; LPL, lipoprotein lipase; STZ, streptozotocin; Tg, transgenic; TG, triglyceride

Supplementary key words cholesteryl ester transfer protein gene expression • insulin • hyperglycemia • experimental diabetes • lipoprotein lipase • triglycerides • nonesterified fatty acids

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