title: Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.
abstract: Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function.
authors.affiliation: From the Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, the Center for Biotechnology and Biomedicine, and.
authors.forename: Uta
authors.initials: U
authors.lastname: Greifenhagen
authors.affiliation: From the Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, the Center for Biotechnology and Biomedicine, and.
authors.forename: Andrej
authors.initials: A
authors.lastname: Frolov
authors.affiliation: the Department of Medicine, Endocrinology, Universität Leipzig, 04103 Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: From the Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, the Center for Biotechnology and Biomedicine, and hoffmann@chemie.uni-leipzig.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D010865:Pilot Projects; D011499:Protein Processing, Post-Translational
chemical_list: D001798:Blood Proteins; D017127:Glycation End Products, Advanced
keywords: Advanced glycation end products; biomarker; glycation; mass spectrometry (MS); post-translational modification (PTM); type 2 diabetes