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 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.
Lin
M C
MC
Department of Metabolic Diseases, Bristol-Myers Squibb, Princeton, NJ 08543-4000, USA.
Gordon
D
D
Wetterau
J R
JR
D002352:Carrier Proteins / Q000235:genetics* / Q000493:pharmacokinetics; D053480:Cholesterol Ester Transfer Proteins; D003864:Depression, Chemical; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006023:Glycoproteins; D006207:Half-Life; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007535:Isomerases / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D019704:Protein Disulfide-Isomerases; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides; D014407:Tumor Cells, Cultured
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D007328:Insulin; D010446:Peptide Fragments; D012333:RNA, Messenger; D014280:Triglycerides; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; D005947:Glucose