Interleukin-1 beta targeted therapy for type 2 diabetes.
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.
Maedler
Kathrin
K
University of Bremen, Centre for Biomolecular Interactions Bremen, Islet Biology Laboratory, 28359 Bremen, Germany. kmaedler@uni-bremen.de
Dharmadhikari
Gitanjali
G
Schumann
Desiree M
DM
Størling
Joachim
J
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018450:Disease Progression; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D009765:Obesity / Q000378:metabolism; D015398:Signal Transduction
D053583:Interleukin-1beta; D005947:Glucose