Document Detail


Prevention of type 1 diabetes: from the view point of beta cell damage.
MedLine Citation:
PMID:  15563975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The hallmark of immune-mediated type 1 diabetes is T cell-mediated destruction of the insulin-producing beta cells in the islets, which results from an imbalance between disease promoting factors and protective elements. The precise mechanisms of beta cell destruction leading to diabetes remain unclear. There are many molecules, including Fas ligand (FasL) and cytokines, such as IL-1, TNF-alpha and IFN-gamma that cause release of other cytokine-mediators that have potential to damage the beta cells. The beta cell-death appears to ultimately be caused by receptor (Fas/FasL)-mediated mechanisms and/or by secretion of cytotoxic molecules (e.g., granzymes, perforin). FasL-mediated beta cell damage might play a role in promoting insulitis and beta cell destruction in autoimmune diabetes in addition to toxic molecules, such as reactive oxygen species (superoxide, hydroxy radical, nitric oxide) or perforin. Furthermore, DNA damage in beta cells leads to poly (ADP-ribose) polymerase-activation which will increase NAD consumption and rapid depletion of NAD compromise ATP production in the cells. Nicotinamide inhibits poly (ADP-ribose) polymerase and reduces nitric oxide accumulation in the NOD pancreas and protect beta cells against radical-induced necrosis. Transgenic mice with beta cell specific overexpression of copper, zinc superoxide dismutase, or thioredoxin are resistant to autoimmune and STZ-induced diabetes. It is apparent that a number of different mechanisms of beta cell destruction are operative in type 1 diabetes. Blockage of multiple pathways, rather than a single pathway, of beta cell-death may, therefore be necessary to fully protect beta cells from destruction and thereby prevent type 1 diabetes.
Authors:
Eiji Kawasaki; Norio Abiru; Katsumi Eguchi
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Diabetes research and clinical practice     Volume:  66 Suppl 1     ISSN:  0168-8227     ISO Abbreviation:  Diabetes Res. Clin. Pract.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-26     Completed Date:  2005-05-12     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8508335     Medline TA:  Diabetes Res Clin Pract     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  S27-32     Citation Subset:  IM    
Affiliation:
Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. eijikawa@net.nagasaki-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Diabetes Mellitus, Type 1 / pathology*,  prevention & control*
Humans
Islets of Langerhans / drug effects,  pathology*
Mice
Mice, Inbred NOD
Oxidative Stress
Chemical
Reg. No./Substance:
0/Antioxidants

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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