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AIMS/HYPOTHESIS:Microvascular complications in the heart and kidney are strongly associated with an overall rise in inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory molecule that limits and resolves inflammation. In this study, we have used a bedside to bench approach to investigate: (1) ANXA1 levels in individuals with type 1 diabetes; (2) the role of endogenous ANXA1 in nephropathy and cardiomyopathy in experimental type 1 diabetes; and (3) whether treatment with human recombinant ANXA1 attenuates nephropathy and cardiomyopathy in a murine model of type 1 diabetes. METHODS:ANXA1 was measured in plasma from individuals with type 1 diabetes with or without nephropathy and healthy donors. Experimental type 1 diabetes was induced in mice by injection of streptozotocin (STZ; 45 mg/kg i.v. per day for 5 consecutive days) in C57BL/6 or Anxa1 -/- mice. Diabetic mice were treated with human recombinant (hr)ANXA1 (1 μg, 100 μl, 50 mmol/l HEPES; 140 mmol/l NaCl; pH 7.4, i.p.) or vehicle (100 μl, 50 mmol/l HEPES; 140 mmol/l NaCl; pH 7.4, i.p.). RESULTS:Plasma levels of ANXA1 were elevated in individuals with type 1 diabetes with/without nephropathy compared with healthy individuals (66.0 ± 4.2/64.0 ± 4 ng/ml vs 35.9 ± 2.3 ng/ml; p 

Original publication

DOI

10.1007/s00125-017-4469-y

Type

Journal article

Journal

Diabetologia

Publication Date

02/2018

Volume

61

Pages

482 - 495

Addresses

Queen Mary University of London, Barts and The London School of Medicine & Dentistry, The William Harvey Research Institute, Charterhouse Square, London, EC1M 6BQ, UK.

Keywords

Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Disease Models, Animal, p38 Mitogen-Activated Protein Kinases, Annexin A1, Blotting, Western, Enzyme-Linked Immunosorbent Assay, Phosphorylation, Male, Proto-Oncogene Proteins c-akt