MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN (MTP) REGULATION IN HEPG2 CELLS - INSULIN NEGATIVELY REGULATES MTP GENE-EXPRESSION

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 mod ulate lipid and lipoprotein metabolism were tested for their ability t o regulate MTP levels in HepG2 cells. Of the factors tested, only insu lin (greater than or equal to 10(-9) M), and high concentrations of gl ucose (>30 mM) were found to decrease MTP large subunit mRNA levels. O leate and glucagon had no effect on MTP mRNA levels. The insulin effec t was dose- and time-dependent and was mediated through the insulin re ceptor. In addition, insulin also decreased protein disulfide isomeras e (the small subunit of MTP) mRNA levels, although to a lesser extent. Due to the slow turnover rate of MTP (t(1/2) = 4.4 days), short-term insulin treatment (24 h) did not change MTP activity levels, indicatin g that the regulation of MTP mRNA levels by insulin is unrelated to in sulin's acute inhibition of apoB secretion in HepG2 cells. In summary, MTP mRNA levels are acutely regulated by insulin in HepG2 cells; howe ver, sustained changes in MTP mRNA levels would be required to affect MTP protein levels.