Insulin suppresses apolipoprotein(a) synthesis by primary cultures of cynomolgus monkey hepatocytes.

Raised plasma lipoprotein(a) (lp(a)) concentrations have been reported in patients with Type I (insulin-dependent) diabetes mellitus, which were lowered by insulin therapy. To investigate the biochemical background of these changes, we studied the effect of insulin on apolipoprotein(a) (apo(a)) synthesis and mRNA levels in primary cultures of cynomolgus monkey hepatocytes. Low concentrations of insulin (10 nmol/l) had a small but significant decreasing effect (p < 0.046) on apolipoprotein(a) secretion (-16%). Maximum inhibition (-33%) was obtained after incubation for 72 h with 1000 nmol/l insulin. Apolipoprotein B-100 secretion was 30%-36% decreased when using 10-1000 nmol/l and no change was observed for the secretion of apolipoprotein A-1 and albumin which were measured as control proteins. Steady state apolipoprotein(a) mRNA concentrations paralleled the decrease in apolipoprotein(a) synthesis (-29% after incubating the cells for 48 h with 100 nmol/l insulin) indicating that the decreased synthesis is regulated at the (post)-transcriptional level. Concentrations of apolipoprotein B-100 and apolipoprotein A-1 mRNA were not changed after incubation with insulin. We conclude that high concentrations of insulin suppress apolipoprotein(a) synthesis in monkey hepatocytes at the (post)-transcriptional level. These data may provide an explanation for the increased plasma concentrations of lipoprotein(a) as found in patients with insulin dependent diabetes mellitus.