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Journal of Lipid Research, Vol 36, 1073-1081, Copyright © 1995 by Lipid Research, Inc.
MC Lin, D Gordon and JR Wetterau
The microsomal triglyceride transfer protein (MTP) is a heterodimeric lipid
transfer protein that is required for the assembly and secretion of
apoB-containing lipoproteins. In this study, four factors that modulate
lipid and lipoprotein metabolism were tested for their ability to regulate
MTP levels in HepG2 cells. Of the factors tested, only insulin (> or =
10(-9) M), and high concentrations of glucose (> 30 mM) were found to
decrease MTP large subunit mRNA levels. Oleate and glucagon had no effect
on MTP mRNA levels. The insulin effect was dose- and time-dependent and was
mediated through the insulin receptor. In addition, insulin also decreased
protein disulfide isomerase (the small subunit of MTP) mRNA levels,
although to a lesser extent. Due to the slow turnover rate of MTP (t1/2 =
4.4 days), short-term insulin treatment (24 h) did not change MTP activity
levels, indicating that the regulation of MTP mRNA levels by insulin is
unrelated to insulin's acute inhibition of apoB secretion in HepG2 cells.
In summary, MTP mRNA levels are acutely regulated by insulin in HepG2
cells; however, sustained changes in MTP mRNA levels would be required to
affect MTP protein levels.
ARTICLES
Microsomal triglyceride transfer protein (MTP) regulation in HepG2 cells: insulin negatively regulates MTP gene expression
Department of Metabolic Diseases, Bristol-Myers Squibb, Princeton, NJ 08543-4000, USA.
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