Hyperinsulinemia is associated with increased production rate of intestinal apolipoprotein B-48 - Containing lipoproteins in humans

Objectives - Whereas postprandial hyperlipidemia is a well-described feature of insulin-resistant states and type 2 diabetes, no previous studies have examined intestinal lipoprotein production rates (PRs) in relation to hyperinsulinemia or insulin resistance in humans. Methods and Results - Apolipoprotein B-48 (apoB-48)-containing lipoprotein metabolism was examined in the steady-state fed condition with a 15-hour primed constant infusion of [D3]-L-leucine in 14 nondiabetic men with a broad range of body mass index (BMI) and insulin sensitivity. To examine the relationship between indices of insulin resistance and intestinal lipoprotein PR data were analyzed in 2 ways: by correlation and by comparing apoB-48 PRs in those whose fasting plasma insulin concentrations were above or below the median for the 14 subjects studied (60 pmol/L). ApoB-48 PR was significantly higher in hyperinsulinemic, insulin- resistant subjects (1.73 +/- 0.39 versus 0.88 +/- 0.13 mg/kg per day; P < 0.05) and correlated with fasting plasma insulin concentrations (r = 0.558; P = 0.038), despite great heterogeneity in apoB-48 kinetic parameters, particularly among the obese subjects. There was no significant difference in clearance of apoB-48 between the 2 groups, nor was there a significant correlation between apoB-48 fractional clearance rate and fasting insulin or homeostasis model assessment-insulin resistance. Conclusions - These are the first human data to conclusively demonstrate that intestinal apoB-48-containing triglyceriderich lipoprotein PR is increased in hyperinsulinemic, insulin-resistant humans. Intestinal lipoprotein particle overproduction is a newly described feature of insulin resistance in humans.