Metabolic basis of hypotriglyceridemic effects of insulin in normal men.
The mechanism by which acute insulin administration alters VLDL apolipoprotein (apo) B subclass metabolism and thus plasma triglyceride concentration was evaluated in 7 normolipidemic healthy men on two occasions, during a saline infusion and during an 8.5-hour euglycemic hyperinsulinemic clamp (serum insulin, 490 +/- 30 pmol/L). During the insulin infusion, plasma triglycerides decreased by 22% (P < .05), and serum free fatty acid decreased by 85% (P < .05). The plasma concentration of VLDL1 apo B fell 32% during the insulin infusion, while that of VLDL2 apo B remained constant. A bolus injection of [3-(2)H]leucine was given on both occasions to trace apo B kinetics in the VLDL1 and VLDL2 subclasses (Svedberg flotation rate, 60-400 and 20-60, respectively), and the kinetic basis for the change in VLDL levels caused by insulin was examined using a non-steady-state multicompartmental model. The mean rate of VLDL1 apo B synthesis decreased significantly by 35% (P < .05) after 0.5 hour of the insulin infusion (523 +/- 87 mg/d) compared with the saline infusion (808 +/- 91 mg/d). This parameter was allowed to vary with time to explain the fall in VLDL1 concentration. After 8.5 hours of hyperinsulinemia, the rate of VLDL1 apo B synthesis was 51% lower (321 +/- 105 mg/d) than during the saline infusion (651 +/- 81 mg/d, P < .05). VLDL2 apo B production was similar during the saline (269 +/- 35 mg/d) and insulin (265 +/- 37 mg/d) infusions. No significant changes were observed in the fractional catabolic rates of either VLDL1 or VLDL2 apo B. We conclude that acute hyperinsulinemia lowers plasma triglyceride and VLDL levels principally by suppressing VLDL1 apo B production but has no effect on VLDL2 apo B production. These findings indicate that the rates of VLDL1 and VLDL2 apo B production in the liver are independently regulated.
Malmström
R
R
Department of Medicine, University of Helsinki, Finland.
Packard
C J
CJ
Watson
T D
TD
Rannikko
S
S
Caslake
M
M
Bedford
D
D
Stewart
P
P
Yki-Järvinen
H
H
Shepherd
J
J
Taskinen
M R
MR
D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D001055:Apolipoproteins B / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood*
D001053:Apolipoproteins; D001055:Apolipoproteins B; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008071:Lipoprotein Lipase