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

AbstractOBJECTIVE:
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 triglyceride-rich lipoprotein PR is increased in hyperinsulinemic, insulin-resistant humans. Intestinal lipoprotein particle overproduction is a newly described feature of insulin resistance in humans.
AuthorsHélène Duez, Benoît Lamarche, Kristine D Uffelman, René Valero, Jeffrey S Cohn, Gary F Lewis
JournalArteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 26 Issue 6 Pg. 1357-63 (Jun 2006) ISSN: 1524-4636 [Electronic] United States
PMID16614317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Apolipoprotein B-48
  • Apolipoproteins
  • Apolipoproteins B
  • Insulin
  • Lipids
  • Lipoproteins
  • Triglycerides
Topics
  • Adult
  • Apolipoprotein B-48
  • Apolipoproteins (blood)
  • Apolipoproteins B (analysis, biosynthesis, blood)
  • Eating
  • Fasting (blood)
  • Homeostasis
  • Humans
  • Hyperinsulinism (metabolism, physiopathology)
  • Insulin (blood)
  • Insulin Resistance
  • Intestinal Mucosa (metabolism)
  • Lipids (blood)
  • Lipoproteins (biosynthesis, blood, chemistry)
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Triglycerides (blood)

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