title: Glycated albumin with loss of fatty acid binding capacity contributes to enhanced arachidonate oxygenation and platelet hyperactivity: relevance in patients with type 2 diabetes.
abstract: High plasma concentrations of nonesterified fatty acids (NEFAs), transported bound to serum albumin, are associated with type 2 diabetes (T2D). The effects of albumin on platelet function were investigated in vitro. Modifications of albumin, such as those due to glycoxidation, were found in patients with T2D, and the consequences of these modifications on biological mechanisms related to NEFA handling were investigated. Mass spectrometry profiles of albumin from patients with T2D differed from those from healthy control subjects. Diabetic albumin showed impaired NEFA binding capacity, and both structural and functional alterations could be reproduced in vitro by incubating native albumin with glucose and methylglyoxal. Platelets incubated with albumin isolated from patients with T2D aggregated approximately twice as much as platelets incubated with albumin isolated from healthy control subjects. Accordingly, platelets incubated with modified albumin produced significantly higher amounts of arachidonate metabolites than did platelets incubated with control albumin. We concluded that higher amounts of free arachidonate are made available for the generation of active metabolites in platelets when the NEFA binding capacity of albumin is blunted by glycoxidation. This newly described mechanism, in addition to hypoalbuminemia, may contribute to platelet hyperactivity and increased thrombosis, known to occur in patients with T2D.
authors.affiliation: Centre de Recherche INSERM UMR 866, Lipides, Nutrition, Cancer, Faculté de Médecine, Université de Bourgogne, Dijon, France dblache@u-bourgogne.fr.
authors.forename: Denis
authors.initials: D
authors.lastname: Blache
authors.affiliation: Centre de Recherche INSERM UMR 866, Lipides, Nutrition, Cancer, Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourdon
authors.affiliation: Clinical and Innovation Plateforme de Protéomique, Centre Hospitalier Universitaire, Dijon, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Salloignon
authors.affiliation: Clinical and Innovation Plateforme de Protéomique, Centre Hospitalier Universitaire, Dijon, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Lucchi
authors.affiliation: Clinical and Innovation Plateforme de Protéomique, Centre Hospitalier Universitaire, Dijon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ducoroy
authors.affiliation: Centre de Recherche INSERM UMR 866, Lipides, Nutrition, Cancer, Faculté de Médecine, Université de Bourgogne, Dijon, France Service Endocrinologie, Diabétologie et Maladies Métaboliques, Centre Hospitalier Universitaire, Dijon, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Petit
authors.affiliation: Centre de Recherche INSERM UMR 866, Lipides, Nutrition, Cancer, Faculté de Médecine, Université de Bourgogne, Dijon, France Service Endocrinologie, Diabétologie et Maladies Métaboliques, Centre Hospitalier Universitaire, Dijon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Verges
authors.affiliation: Centre de Recherche INSERM UMR 866, Lipides, Nutrition, Cancer, Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D015539:Platelet Activation; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D000093423:Glycated Serum Albumin
chemical_list: D005230:Fatty Acids, Nonesterified; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D016718:Arachidonic Acid; D000093423:Glycated Serum Albumin