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


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.
Duez
Hélène
H
Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Ontario, Canada.
Lamarche
Benoît
B
Uffelman
Kristine D
KD
Valero
René
R
Cohn
Jeffrey S
JS
Lewis
Gary F
GF
D000328:Adult; D053283:Apolipoprotein B-48; D001053:Apolipoproteins / Q000097:blood; D001055:Apolipoproteins B / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D004435:Eating; D005215:Fasting / Q000097:blood; D006706:Homeostasis; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000096:biosynthesis* / Q000097:blood / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D014280:Triglycerides / Q000097:blood
D053283:Apolipoprotein B-48; D001053:Apolipoproteins; D001055:Apolipoproteins B; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides