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Interleukin-Targeted Therapy for Metabolic Syndrome and Type 2 Diabetes

  • Kathrin MaedlerEmail author
  • Gitanjali Dharmadhikari
  • Desiree M. Schumann
  • Joachim Størling
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 203)

Abstract

Interleukin-1β (IL-1β) is a key regulator of the body’s inflammatory response and is produced after infection, injury, and an antigenic challenge. Cloned in 1984, the single polypeptide IL-1β has been shown to exert numerous biological effects. It plays a role in various diseases, including autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, and Type 1 diabetes, as well as in diseases associated with metabolic syndrome such as atherosclerosis, chronic heart failure, and Type 2 diabetes. The macrophage is the primary source of IL-1β, but epidermal, epithelial, lymphoid, and vascular tissues also synthesize IL-1. Recently, IL-1β production and secretion have also been reported from pancreatic islets. Insulin-producing β-cells within the pancreatic islets are specifically prone to IL-β-induced destruction and loss of function. Macrophage-derived IL-1β production in insulin-sensitive organs leads to the progression of inflammation and induction of insulin resistance in obesity. This chapter explains the mechanisms involved in the inflammatory response during diabetes progression with specific attention to the IL-1β signal effects influencing insulin action and insulin secretion . We highlight recent clinical studies, rodent and in vitro experiments with isolated islets using IL-1β as a potential target for the therapy of Type 2 diabetes.

Keywords

β-Cell IL-1β Diabetes Inflammation Obesity Interleukin-1 receptor antagonist 

Notes

Acknowledgments

This work was supported by the German Research Foundation (DFG, Emmy Noether Programm, MA4172/1-1), the Juvenile Diabetes Research Foundation (JDRF 26-2008-861), and the European Foundation for the Study of Diabetes (EFSD)/Merck Sharp & Dohme (MSD) European Studies on Beta Cell Function and Survival. The authors thank the members of the Islet Biology laboratory in Bremen for critical discussion.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Kathrin Maedler
    • 1
    Email author
  • Gitanjali Dharmadhikari
    • 1
  • Desiree M. Schumann
    • 2
  • Joachim Størling
    • 3
  1. 1.Centre for Biomolecular Interactions BremenUniversity of BremenBremenGermany
  2. 2.Boehringer-IngelheimCardiometabolic Diseases ResearchBiberachGermany
  3. 3.Hagedorn Research InstituteGentofteDenmark

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