Insulin suppression of VLDL apo B secretion is not mediated by the LDL receptor.
Insulin inhibits hepatic very low density lipoprotein (VLDL) apo B secretion in rats. Current studies test whether the insulin effect is LDL receptor-mediated by examining the effect of insulin on VLDL apo B secretion in hepatocytes derived from Ldlr-/- and control mice. Primary hepatocytes were incubated overnight with media containing 14C-leucine and either 0.1nM (basal) or 200nM insulin. Afterwards, secreted VLDL B100 and B48 were quantitated. Insulin reduced 14C-labeled B100 and B48 comparably in control and Ldlr-/- hepatocytes with a 62+/-12% vs. 59+/-12% decrease in B100, and a 56+/-11% vs. 61+/-9% decrease in B48. Results indicate: (1) mouse hepatocytes respond to insulin by reducing VLDL apo B output; (2) both VLDL B100 and B48 secretion are suppressed; and (3) insulin inhibition of VLDL apo B secretion is retained in Ldlr-/- hepatocytes.
Chirieac
Doru V
DV
Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, P.O. Box 626, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Cianci
Joanne
J
Collins
Heidi L
HL
Sparks
Janet D
JD
Sparks
Charles E
CE
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000378:metabolism*
D001055:Apolipoproteins B; D007328:Insulin; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL