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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0293v1 200/1/45    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kopprasch, S. Articles by Bornstein, S. Search for Related Content PubMed PubMed Citation Articles by Kopprasch, S. Articles by Bornstein, S.

S Kopprasch, Department of Internal Medicine 3, University of Technology Dresden, Carl Gustav Carus Medical School, Dresden, Germany
J Pietzsch, Department of Radiopharmaceutical Biology, Institute of Radiopharmacy, Research Center Dresden-Rossendorf, Dresden, Germany
I Ansurudeen, Carl Gustav Carus Medical School, Department of Internal Medicine 3, University of Technology Dresden, Dresden, Germany
J Graessler, Carl Gustav Carus Medical School, Department of Internal Medicine 3, University of Technology Dresden, Dresden, Germany
A Krug, Carl Gustav Carus Medical School, Department of Internal Medicine 3, University of Technology Dresden, Dresden, Germany
M Ehrhart-Bornstein, Dresden, Germany
S Bornstein, Carl Gustav Carus Medical School, Department of Internal Medicine 3, University of Technology Dresden, Dresden, Germany

Correspondence: Steffi Kopprasch, Email: Steffi.Kopprasch{at}uniklinikum-dresden.de

Abstract

Modification of low density lipoprotein (LDL) and abnormal aldosterone and cortisol metabolism have been implicated in the pathogenesis of type 2 diabetes (DM2) and diabetic vascular disease. Since LDL serves as a major cholesterol source for adrenal steroidogenesis we investigated whether LDL modification in prediabetic and diabetic subjects influences adrenocortical aldosterone and cortisol release. LDL was isolated from 30 subjects with normal glucose tolerance (NGT-LDL), 30 subjects with impaired glucose tolerance (IGT-LDL), and 26 patients with DM2 (DM2-LDL). Oxidation and glycoxidation characteristics of LDL apolipoprotein B100 (apoB100) of each individual was assessed by gas chromatography-mass spectrometry analysis. Human adrenocortical cells (NCI-H295R) were incubated for 24h with 100 µg/mL LDL and after removal of supernatants stimulated for further 24h with angiotensin II (AngII). In supernatants aldosterone and cortisol secretion was measured. IGT-LDL and DM2-LDL were substantially more modified than NGT-LDL. Each of the five measured oxidation/glycoxidation markers was significantly positively associated with glycemic control, measured as HbA1c. LDL from all subjects stimulated both the basal and AngII-induced aldosterone and cortisol release from adrenocortical cells. However, hormone secretion was significantly inversely related to the degree of LDL oxidation/glycoxidation. We conclude that LDL modifications in IGT and DM2 subjects may have significant clinical benefits by counteracting prediabetic and diabetic overactivity of the renin-angiotensin-aldosterone system and enhanced cortisol generation.