Serum Proteome Pool Changes in Type 2 Diabetic Patients Treated with Anakinra
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 HbA1c 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.
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.
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.
Anakinra-induced changes in the serum proteome pool associated with a decreased cardiovascular disease risk, reduced inflammation and improved beta cell secretory function.
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- Author Affiliations
- 1. Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
- 2. University Hospital Zurich and Center for Integrative Human Physiology, Zurich, Switzerland
- 3. CRC MAS, University of Lund, Malmö, Sweden
- 4. Institute for Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- 5. Department of Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
- 6. Department of Translational Diabetology, Hagedorn Research Institute, 1 Niels Steensensvej, DK 2820, Gentofte, Denmark