This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quiñones-Galvan, A. Articles by Ferrannini, E. Search for Related Content PubMed PubMed Citation Articles by Quiñones-Galvan, A. Articles by Ferrannini, E. Related Collections Risk Factors Lipid and lipoprotein metabolism Oxidant stress

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2928.)
© 1999 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Evidence That Acute Insulin Administration Enhances LDL Cholesterol Susceptibility to Oxidation in Healthy Humans

Alfredo Quiñones-Galvan; Anna Maria Sironi; Simona Baldi; Fabio Galetta; Ulisse Garbin; Anna Fratta-Pasini; Luciano Cominacini; Ele Ferrannini

From the CNR Institute of Clinical Physiology and Department of Internal Medicine, University of Pisa, Pisa, Italy, and Istituto di Semeiotica e Nefrologia Medica (U.G., A.F.-P.), University of Verona, Verona, Italy.

Correspondence to Ele Ferrannini, MD, CNR Institute of Clinical Physiology, Via Savi 8, 56126 Pisa, Italy. E-mail ferranni{at}ifc.pi.cnr.it

Abstract—Increased free radical production and hyperinsulinemia are thought to play a role in experimental and human atherosclerosis, but the relation between the 2 abnormalities has not been studied. In 23 healthy volunteers, we measured the susceptibility of circulating low-density lipoprotein (LDL) cholesterol particles to in vitro copper sulfate oxidation (measured as the lag phase) and cell-mediated oxidative modification (measured as malondialdehyde generation in LDL during incubation with human umbilical vein endothelial cells), as well as the vitamin E content of LDL cholesterol at baseline and after 2 hours of physiological hyperinsulinemia (euglycemic insulin clamp). The lag time of LDL oxidation decreased from control values of 108±3 and 107±3 minutes (at baseline and after 2 hours of saline infusion) to 101±3 minutes after 2 hours of clamping (P<0.0001). At corresponding times, cell-mediated malondialdehyde generation in LDL rose from 4.96±0.11 and 4.98±0.10 to 5.28±0.10 nmol/L (P=0.0006), whereas the LDL vitamin E content decreased from 6.78±0.06 and 6.77±0.06 to 6.64±0.06 µg/mg (P<0.04). The insulin-induced shortening of the lag phase was directly related to the decrement of vitamin E in LDL; furthermore, in subjects with higher baseline serum triglyceride levels, insulin induced a greater shortening of the lag phase than in subjects with low baseline triglycerides. We conclude that in healthy humans acute physiological hyperinsulinemia enhances the oxidative susceptibility of LDL cholesterol particles. This effect may have pathogenic significance for atherogenesis in insulin resistant states.

Key Words: insulin • LDL cholesterol • oxidation • free radicals

This article has been cited by other articles:

				T. Weinbrenner, H. Schroder, V. Escurriol, M. Fito, R. Elosua, J. Vila, J. Marrugat, and M.-I. Covas Circulating oxidized LDL is associated with increased waist circumference independent of body mass index in men and women Am. J. Clinical Nutrition, January 1, 2006; 83(1): 30 - 35. [Abstract] [Full Text] [PDF]

				A. Fortuno, G. San Jose, M. U. Moreno, O. Beloqui, J. Diez, and G. Zalba Phagocytic NADPH Oxidase Overactivity Underlies Oxidative Stress in Metabolic Syndrome Diabetes, January 1, 2006; 55(1): 209 - 215. [Abstract] [Full Text] [PDF]