The use of interleukin-1-receptor antagonists in the treatment of diabetes mellitus (original) (raw)

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 240–241 (2008)Cite this article

Decreased functional islet β-cell mass is the main cause of onset and progression of both type 1 and 2 diabetes mellitus. In type 1 diabetes mellitus, β-cell death is predominantly due to an autoimmune-driven, T-cell-mediated inflammatory process in the islets.1 Although the mechanisms of β-cell failure in type 2 diabetes mellitus remain debated, stress and inflammatory pathways have been implicated. For example, metabolic stress caused by repetitive glucose excursions, dyslipidemia and increased levels of adipokines1 can induce an inflammatory response characterized by local cytokine secretion,2 islet immune-cell infiltration,3 β-cell apoptosis, amyloid deposits, and eventual fibrosis. Thus, islet inflammation could be a shared feature of both types of diabetes mellitus, converging on a common pathway that leads to β-cell secretory failure and apoptosis. In this context, interleukin 1β (IL-1β) has emerged as a master cytokine, which regulates islet chemokine production and causes impaired insulin production and β-cell death.4 Preclinical studies of IL-1 antagonism in animal models of both type 1 and type 2 diabetes mellitus have shown promising results.1 In this Viewpoint, we discuss the potential role of anakinra—a recombinant human IL-1-receptor antagonist—in the treatment of diabetes mellitus.

Anakinra is a competitive inhibitor of IL-1 binding to type I IL-1 receptors.5 This agent is currently licensed for the treatment of rheumatoid arthritis unresponsive to other disease-modifying antirheumatic drugs. As IL-1β clearly has a key role in the pathogenesis of diabetes mellitus, the availability of anakinra enabled us to conduct a clinical trial of IL-1 receptor antagonism in patients with type 2 diabetes mellitus.6

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Authors and Affiliations

  1. MY Donath is Attending Physician and Professor, Clinic for Endocrinology and Diabetes, University Hospital Zurich and Center for Integrated Human Physiology, University of Zurich, Switzerland;,
    Marc Y Donath
  2. Department for Translational Diabetology, T Mandrup-Poulsen is Director, Steno Diabetes Center, Gentofte, and Professor, Core Unit for Medical Research Methodology, Institute of Biomedicine, Faculty of Health Sciences, University of Copenhagen, Denmark.,
    Thomas Mandrup-Poulsen

Authors

  1. Marc Y Donath
  2. Thomas Mandrup-Poulsen

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Correspondence toThomas Mandrup-Poulsen.

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The authors declare no competing financial interests.

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Donath, M., Mandrup-Poulsen, T. The use of interleukin-1-receptor antagonists in the treatment of diabetes mellitus.Nat Rev Endocrinol 4, 240–241 (2008). https://doi.org/10.1038/ncpendmet0783

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