Interleukin-1 beta targeted therapy for type 2 diabetes

Expert Opin Biol Ther. 2009 Sep;9(9):1177-88. doi: 10.1517/14712590903136688.

Abstract

Since having been cloned in 1984, IL-1beta has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1beta is a regulator of the body's inflammatory response and is produced after infection, injury, and antigenic challenge. 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. Macrophage are the primary source of IL-1, but epidermal, epithelial, lymphoid and vascular tissues also synthesize IL-1. IL-1beta production and secretion have also been reported from pancreatic islets. Insulin-producing beta-cells within pancreatic islets are specifically prone to IL-beta-induced destruction and loss of function. Macrophage-derived IL-1beta production in insulin-sensitive organs, leads to progression of inflammation and induction of insulin resistance in obesity. We summarize the mechanisms involved in inflammation and specifically the IL-1beta signals that lead to the progression of insulin resistance and diabetes. We highlight recent clinical studies and experiments in animals and isolated islets using IL-1beta as a potential target for the therapy of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • Brain / metabolism
  • Cell Death / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Disease Progression
  • Glucose / pharmacology
  • Humans
  • Insulin Resistance
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / metabolism*
  • Liver / metabolism
  • Mice
  • Models, Animal
  • Obesity / metabolism
  • Signal Transduction

Substances

  • Interleukin-1beta
  • Glucose