Serum Proteome Pool Changes in Type 2 Diabetic Patients Treated with Anakinra

Clinical Proteomics

Allan Vaag¹  Jan A. Ehses⁴  Marc Y. Donath⁴  Thomas Mandrup-Poulsen²  James Norton McGuire¹  Mirjam V. Faulenbach⁴  Claus M. Larsen¹  Flemming Pociot³  Mette Koefoed¹ 

[1] Steno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkSteno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark;Steno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkInstitute for Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Medicine and Surgery, Karolinska Institute, Stockholm, SwedenDepartment of Translational Diabetology, Hagedorn Research Institute, Gentofte, DenmarkSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkInstitute for Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Medicine and Surgery, Karolinska Institute, Stockholm, SwedenDepartment of Translational Diabetology, Hagedorn Research Institute, Gentofte, DenmarkInstitute for Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkInstitute for Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Medicine and Surgery, Karolinska Institute, Stockholm, SwedenDepartment of Translational Diabetology, Hagedorn Research Institute, Gentofte, DenmarkDepartment of Medicine and Surgery, Karolinska Institute, Stockholm, SwedenSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkInstitute for Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Medicine and Surgery, Karolinska Institute, Stockholm, SwedenDepartment of Translational Diabetology, Hagedorn Research Institute, Gentofte, DenmarkDepartment of Translational Diabetology, Hagedorn Research Institute, Gentofte, DenmarkSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkInstitute for Biomedical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Medicine and Surgery, Karolinska Institute, Stockholm, SwedenDepartment of Translational Diabetology, Hagedorn Research Institute, Gentofte, Denmark;Steno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkCRC MAS, University of Lund, Malmö, SwedenSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkCRC MAS, University of Lund, Malmö, SwedenCRC MAS, University of Lund, Malmö, SwedenSteno Diabetes Center and Hagedorn Research Institute, Gentofte, DenmarkCRC MAS, University of Lund, Malmö, Sweden;University Hospital Zurich and Center for Integrative Human Physiology, Zurich, SwitzerlandUniversity Hospital Zurich and Center for Integrative Human Physiology, Zurich, SwitzerlandUniversity Hospital Zurich and Center for Integrative Human Physiology, Zurich, Switzerland

关键词: Biomarkers;    Proteomics;    Inflammation;    SELDI-TOF-MS;    Transthyretin;    Retinol binding protein 4;    Transferrin;    Apolipoprotein-AI;   

DOI  :  10.1007/s12014-010-9056-x

来源: Humana Press Inc

【 摘 要 】

Abstract

Introduction

High glucose concentrations induce the production of IL-1β in human pancreatic beta cells leading to impaired insulin secretion, decreased cell proliferation and apoptosis. Blockade of IL-1 signalling with the recombinant human IL-1 receptor antagonist anakinra reduces HbA_1c in patients with type 2 diabetes. The aims of the present study were to identify: (1) candidate surrogates for improved glycemia in type 2 diabetic patients following treatment with anakinra, (2) proteins that change serum concentration because of anakinra treatment and (3) candidate biomarkers that may predict improved glycemia in type 2 diabetic subjects treated with anakinra.

Methods

Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry was used to analyse serum from 67 type 2 diabetic patients who had received either placebo or anakinra for 13 weeks. Immunodepletion with magnetic protein G bead-coupled antibodies were used to identify three proteins and Western blotting confirmed the biomarker concentration pattern of four proteins.

Results

Twelve proteins, including transthyretin (TTR) and transferrin (Tf), were identified as candidate surrogates for improved glycemia. Six proteins, including retinol-binding protein 4 (RPB4) and a protein tentatively identified as modified apolipoprotein-A1 (apo-AI), increased expression as a consequence of anakinra treatment and four proteins were candidate biomarkers that may predict improved glycemia following anakinra treatment. Furthermore, we found increased RBP4 to be associated with improved beta cell secretory function and increased TTR, RBP4 and modified apo-AI (peak at 28,601 Da) to be associated with decreased inflammation.

Conclusions

Anakinra-induced changes in the serum proteome pool associated with a decreased cardiovascular disease risk, reduced inflammation and improved beta cell secretory function.

【 授权许可】

Unknown