Insulin effects on apolipoprotein B lipoprotein synthesis and secretion by primary cultures of rat hepatocytes.
Lipoprotein synthesis and secretion were examined in primary cultures of rat hepatocytes cultured on collagen-coated plates and incubated with pharmacologic and physiologic concentrations of insulin. Media insulin concentration declined rapidly over the course of incubation indicating that hepatocytes rapidly degrade insulin. When insulin was present in the media, cellular triglyceride accumulated while lipid secretion declined. Insulin inhibited the incorporation of labeled amino acids into total secretory lipoprotein apoproteins and apolipoprotein B (apo B) as well as apo B mass as measured by monoclonal radioimmunoassay. The effect of insulin on apo B secretion occurred as early as three hours after the addition of insulin to the culture media and both apo B of higher molecular weight (apo BH) and apo B of lower molecular weight (apo BL) were affected. Cellular apo B did not accumulate within cells. The majority of secretory lipid radioactivity synthesized from acetate was in VLDL density lipoproteins. The composition of newly synthesized lipids as assessed by thin layer chromatography was not significantly altered with insulin. These studies support the finding that insulin inhibits VLDL secretion by hepatocytes while at the same time stimulating overall triglyceride synthesis. A suggested mechanism is that insulin uncouples triglyceride and apo B synthesis, which influences subsequent lipoprotein assembly and secretory pathways. These results are consistent with the concept that postprandial insulin release inhibits hepatic lipoprotein secretion while intestinal lipoprotein metabolic pathways are most active.
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis*; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D000085:Acetates; D000596:Amino Acids; D001055:Apolipoproteins B; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008715:Methionine; D019342:Acetic Acid