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Cholesteryl ester transfer protein expression is down-regulated in hyperinsulinemic transgenic mice
J A Berti1, A C Casquero, P R Patricio
1Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, SP, Brazil.
Journal of Lipid Research
|July 18, 2003
Summary
Insulin deficiency increases cholesteryl ester transfer protein (CETP) levels and liver expression. Insulin therapy and glucose supplementation modulate CETP, suggesting insulin down-regulates CETP gene expression.
Area of Science:
- Biochemistry
- Endocrinology
- Molecular Biology
Background:
- Cholesteryl ester transfer protein (CETP) facilitates lipid redistribution between lipoproteins.
- Understanding CETP regulation is crucial for lipid metabolism and cardiovascular health.
Purpose of the Study:
- To investigate the in vivo regulation of CETP expression by varying insulin levels.
- To determine the impact of insulin deficiency and hyperinsulinemia on CETP expression and activity.
Main Methods:
- Induction of insulin deficiency using streptozotocin (STZ) in transgenic mice.
- Induction of hyperinsulinemia via insulin injections, with and without glucose supplementation.
- Measurement of plasma CETP levels, CE transfer rate, and hepatic CETP mRNA expression.
Main Results:
- STZ treatment significantly increased plasma CETP, hepatic CETP mRNA, and CE transfer rate.
- Insulin replacement in STZ-induced diabetic mice normalized glycemia and hepatic CETP mRNA.
- Glucose supplementation elevated plasma CETP, while combined insulin and glucose reduced hepatic CETP mRNA.
Conclusions:
- Insulin deficiency up-regulates CETP expression and activity.
- Insulin administration down-regulates hepatic CETP gene expression, particularly under conditions of hyperglycemia.
- These findings highlight a significant role for insulin in the regulation of CETP.