Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Viewpoint
  • Published:

The use of interleukin-1-receptor antagonists in the treatment of diabetes mellitus

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

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Donath MY et al. (2007) Cytokines and ß-cell biology: from concept to clinical translation. Endocr Rev [10.1210/er.2007-0033]

  2. Maedler K et al. (2002) Glucose-induced ß cell production of IL1ß contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110: 851–860

    Google Scholar 

  3. Ehses JA et al. (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56: 2356–2370

    Google Scholar 

  4. Dinarello CA (2005) Blocking IL-1 in systemic inflammation. J Exp Med 201: 1355–1359

    Google Scholar 

  5. Dayer-Métroz MD et al. (1989) A natural interleukin 1 (IL-1) inhibitor counteracts the inhibitory effect of IL-1 on insulin production in cultured rat pancreatic islets. J Autoimmun 2: 163–171

    Google Scholar 

  6. Larsen CM et al. (2007) Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 356: 1517–1526

    Google Scholar 

  7. Kolb H and Mandrup-Poulsen T (2005) An immune origin of type 2 diabetes. Diabetologia 48: 1038–1050

    Google Scholar 

  8. Spranger J et al. (2003). Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52: 812–817

    Google Scholar 

  9. Stratton IM et al. (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321: 405–412

    Google Scholar 

  10. Butler AE et al. (2003) ß-cell deficit and increased ß-cell apoptosis in humans with type 2 diabetes. Diabetes 52: 102–110

    Google Scholar 

Download references

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Mandrup-Poulsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Mandrup-Poulsen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0783

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing