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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1357.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Hyperinsulinemia Is Associated With Increased Production Rate of Intestinal Apolipoprotein B-48–Containing Lipoproteins in Humans

Hélène Duez; Benoît Lamarche; Kristine D. Uffelman; René Valero; Jeffrey S. Cohn; Gary F. Lewis

From the Departments of Medicine and Physiology (H.D., K.D.U., R.V., G.F.L.), Division of Endocrinology and Metabolism, University of Toronto, Ontario, Canada; Institut des nutraceutiques et aliments fonctionnels (B.L.), Université Laval, Québec, Canada; and Clinical Research Institute of Montreal (J.S.C.), Canada. Present address for J.S.C.: Heart Research Institute, Nutrition and Metabolism Group, Camperdown, Sydney, NSW 2050, Australia.

Correspondence to Dr Gary F. Lewis, Toronto General Hospital, 200 Elizabeth St, EN12-218, Toronto, Ontario, M5G 2C4. E-mail gary.lewis{at}uhn.on.ca

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 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.

In the present study, we investigated whether intestinal lipoprotein particle production rate is related to indices of insulin resistance in humans. ApoB-48–containing lipoprotein metabolism was examined in 14 nondiabetic men with a broad range of BMI and insulin sensitivity. We demonstrate that intestinal apoB-48–containing TRL production rate is increased in hyperinsulinemic, insulin-resistant humans.

Key Words: lipoprotein • intestinal • insulin resistance • hyperinsulinemia • stable isotype kinetic • triglyceride

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