J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on October 1, 2003

Papers In Press, published online ahead of print July 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300036-JLR200
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Submitted on January 24, 2003
Revised on June 20, 2003
Accepted on July 7, 2003

Cholesteryl ester transfer protein expression is downregulated in hyperinsulinemic transgenic mice

Jairo A. Berti, Andrea C. Casquero, Patrícia R. Patrício, Eliete J. B. Bighetti, Everardo M. Carneiro, Antonio C. Boschero, and Helena C. F. Oliveira

Depto. de Fisiologia e Biofisica, Universidade Estadual de Campinas, Campinas, Sao Paulo 13083-970

Corresponding Author: ho98{at}unicamp.br

CETP mediates cholesteryl ester and triglyceride redistribution among plasma lipoproteins. In this work we investigated whether varying levels of insulin regulates the CETP expression in vivo. Insulin deficiency (streptozotocin injection, STZ) 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 to 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 hyperinsulinemic INS+GLUC mice. Hepatic CETP mRNA was not altered in GLUC mice and was reduced by 1/3 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 downregulates CETP gene expression.


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P. S. MacLean, S. Vadlamudi, K. G. MacDonald, W. J. Pories, and H. A. Barakat
Suppression of Hepatic Cholesteryl Ester Transfer Protein Expression in Obese Humans with the Development of Type 2 Diabetes Mellitus
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2250 - 2258.
[Abstract] [Full Text] [PDF]


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