title: Effects of insulin and acipimox on VLDL1 and VLDL2 apolipoprotein B production in normal subjects.
abstract: The objective of the study was to examine the potential differential effect of insulin and acipimox (both of which reduce free fatty acid [FFA] availability) on VLDL apolipoprotein (apo) B metabolism. We studied eight healthy men (age 40 +/- 4 years, BMI 25.8 +/- 0.9 kg/m2, plasma triglycerides 1.30 +/- 0.12 mmol/l) after an overnight fast (control study, n = 8), during inhibition of lipolysis with an antilipolytic agent, acipimox (n = 8), and under 8.5-h euglycemic-hyperinsulinemic conditions (n = 5). Plasma FFAs were similarly suppressed in the acipimox and insulin studies (approximately 70% suppression). 2H3-leucine was used to trace apo B kinetics in VLDL1 and VLDL2 subclasses (Svedberg flotation rates: 60-400 and 20-60), and a non-steady-state multicompartmental model was used to derive the kinetic constants. The mean rate of VLDL1 apo B production was 708 +/- 106 mg/day at the beginning and 602 +/- 140 mg/day at the end of the control study. Production of the lipoprotein decreased to 248 +/- 93 mg/day during the insulin study (P < 0.05 vs. control study) and to 375 +/- 92 mg/day (NS) during the acipimox study. Mean VLDL2 apo B production was significantly increased during the acipimox study (399 +/- 42 vs. 236 +/- 27 mg/day, acipimox vs. control, P < 0.05) but not during the insulin study (332 +/- 51 mg/day, NS). The fractional catabolic rates of VLDL1 and VLDL2 apo B were similar in all three studies. We conclude that acute lowering of FFAs does not change the overall production rate of VLDL particles, but there is a shift toward production of smaller and denser VLDL2 particles, and, thus, the amount of total VLDL particles secreted remained constant. Insulin acutely suppresses the total production rate of VLDL apo B by decreasing the production of large triglyceride-rich VLDL1 particles. Based on these findings, we postulate that insulin has a direct suppressive effect on the production of VLDL apo B in the liver, independent of the availability of FFAs.
authors.affiliation: Department of Medicine, University of Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Malmström
authors.forename: C J
authors.initials: CJ
authors.lastname: Packard
authors.forename: M
authors.initials: M
authors.lastname: Caslake
authors.forename: D
authors.initials: D
authors.lastname: Bedford
authors.forename: P
authors.initials: P
authors.lastname: Stewart
authors.forename: H
authors.initials: H
authors.lastname: Yki-Järvinen
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000096:biosynthesis*; D001055:Apolipoproteins B / Q000096:biosynthesis*; D001786:Blood Glucose / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D012016:Reference Values
chemical_list: D001053:Apolipoproteins; D001055:Apolipoproteins B; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D007328:Insulin; D008055:Lipids; D008079:Lipoproteins, VLDL; D011719:Pyrazines; C027610:apolipoprotein VLDL II; C027696:acipimox