Effects of insulin on lipoprotein secretion in rat hepatocyte cultures. The role of the insulin receptor.
Insulin inhibits the secretion of lipoprotein components such as triglyceride, phospholipid, and apolipoproteins B and E in primary rat hepatocyte cultures. The aim of this study was to determine whether these hormonal effects are related to the interaction of insulin with its receptor on the surface of cultured hepatocytes. Half-maximal inhibition of secretion of apolipoprotein E and triglyceride occurred at 6 ng/ml porcine insulin, equivalent to a 20% receptor occupancy. When compared to porcine insulin, both guinea pig insulin and desoctapeptide insulin were 60 times less inhibitory on triglyceride and apolipoprotein secretion. These analogs were also 60 times less effective in competing with porcine 125I-insulin for receptor binding. Anti-insulin receptor IgG inhibited binding of porcine insulin to cells in a dose-dependent fashion. However, similar to the hormone itself, it reduced the secretion of triglyceride and apolipoproteins E and B. Preincubation of cells with 200 ng/ml porcine insulin for 15 h caused a 2.5-fold reduction of surface receptor number. These cells were less sensitive to the inhibitory effect of porcine insulin on secretion of triglyceride and apolipoproteins B and E. We conclude that the effects of insulin on lipoprotein processing by hepatocytes in culture are receptor-mediated, can be imitated by antibodies, to the insulin receptor, and are subject to control by receptor down-regulation.
D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D007074:Immunoglobulin G; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D013552:Swine; D014280:Triglycerides / Q000378:metabolism
D000345:Affinity Labels; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D007074:Immunoglobulin G; D007328:Insulin; D008074:Lipoproteins; D014280:Triglycerides; D011972:Receptor, Insulin