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Reviews in Endocrine and Metabolic Disorders

Published in:

01-12-2008

Mass spectrometric quantification of amino acid oxidation products identifies oxidative mechanisms of diabetic end-organ damage

Authors: Anuradha Vivekanadan-Giri, Jeffrey H. Wang, Jaeman Byun, Subramaniam Pennathur

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 4/2008

Abstract

Diabetes mellitus is increasingly prevalent worldwide. Diabetic individuals are at markedly increased risk for premature death due to cardiovascular disease. Furthermore, substantial morbidity results from microvascular complications which include retinopathy, nephropathy, and neuropathy. Clinical studies involving diabetic patients have suggested that degree of diabetic hyperglycemia correlates with risk of complications. Recent evidence implicates a central role for oxidative stress and vascular inflammation in all forms of insulin resistance, obesity, diabetes and its complications. Although, glucose promotes glycoxidation reactions in vitro and products of glycoxidation and lipoxidation are elevated in plasma and tissue in diabetics, the exact relationships among hyperglycemia, the diabetic state, and oxidative stress are not well-understood. Using a combination of in vitro and in vivo experiments, we have identified amino acid oxidation markers that serve as molecular fingerprints of specific oxidative pathways. Quantification of these products utilizing highly sensitive and specific gas chromatography/mass spectrometry in animal models of diabetic complications and in humans has provided insights in oxidative pathways that result in diabetic complications. Our studies strongly support the hypothesis that unique oxidants are generated in the microenvironment of tissues vulnerable to diabetic damage. Potential therapies interrupting these reactive pathways in target tissue are likely to be beneficial in preventing diabetic complications.

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Title: Mass spectrometric quantification of amino acid oxidation products identifies oxidative mechanisms of diabetic end-organ damage
Authors: Anuradha Vivekanadan-Giri
Jeffrey H. Wang
Jaeman Byun
Subramaniam Pennathur
Publication date: 01-12-2008
Publisher: Springer US
Published in: Reviews in Endocrine and Metabolic Disorders / Issue 4/2008
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-008-9093-1

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Other articles of this Issue 4/2008

β-cell failure as a complication of diabetes

Novel mechanisms of protein synthesis in diabetic nephropathy—role of mRNA translation

New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy

Mechanisms of disease: The oxidative stress theory of diabetic neuropathy

Proteoglycan mediated lipoprotein retention: A mechanism of diabetic atherosclerosis

Defining human diabetic nephropathy on the molecular level: Integration of transcriptomic profiles with biological knowledge

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At a glance: The STEP trials