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Originally published In Press as doi:10.1194/jlr.M700551-JLR200 on April 12, 2008

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Journal of Lipid Research, Vol. 49, 1438-1444, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Soluble lectin-like oxidized low density lipoprotein receptor-1 in type 2 diabetes mellitus

Kathryn C. B. Tan1,*, Sammy W. M. Shiu*, Ying Wong*, Lin Leng{dagger} and Richard Bucala{dagger}

* Department of Medicine, University of Hong Kong, Hong Kong, China
{dagger} Departments of Medicine and Pathology, Yale University School of Medicine, New Haven, CT

This study was supported by funding from the Hong Kong Research Grants Council (Grant HKU 7585/05M).

Published, JLR Papers in Press, April 12, 2008.

1 To whom correspondence should be addressed. e-mail: kcbtan{at}hkucc.hku.hk

The lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) can be proteolytically cleaved and released as soluble forms (sLOX-1). We have determined serums LOX-1 in type 2 diabetes and evaluated the effect of glucose and advanced glycation end products (AGEs) on sLOX-1 in vitro and in vivo. Endothelial cells were incubated with glucose or AGEs, and sLOX-1 in cell medium was measured. Serum sLOX-1 was measured in 219 diabetic patients and 187 controls by ELISA. The effect of lowering glucose and AGEs on sLOX-1 was determined in 38 poorly controlled diabetic patients after improvement in glycemic control. Incubation of endothelial cells with AGE-BSA led to a dose-dependent increase in sLOX-1, whereas the effect of glucose on sLOX-1 was less marked. Serum sLOX-1 was 9% higher in diabetic patients compared with controls (P < 0.01). In the poorly controlled patients, serum sLOX-1 decreased by 12.5% after improvement in glycemic control (P < 0.05). The magnitude of reduction in sLOX-1 correlated with the improvement in hemoglobin A1c and AGEs but not with the reduction in oxidized LDL.XXX sLOX-1 level is increased in type 2 diabetes. Both glucose and AGEs are important determinants of LOX-1 expression, and lowering glucose and AGEs leads to a reduction in sLOX-1.

Supplementary key words advanced glycation end products • oxidized LDL • soluble receptors


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