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 C-14-leucine and either 0.1 nM (basal) or 200 nM insulin. Afterwards, secreted VLDL B100 and B48 were quantitated. Insulin reduced C-14-labeled B100 and B48 comparably in control and Ldlr-/- hepatocytes with a 62 +/- 12% vs. 59 12% decrease in B 100, 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 B 100 and B48 secretion are suppressed; and (3) insulin inhibition of VLDL apo B secretion is retained in Ldlr-/- hepatocytes. (C) 2002 Elsevier Science (USA). All rights reserved.