Document Detail


Interdiction of the diabetic state in NOD mice by sustained induction of heme oxygenase: possible role of carbon monoxide and bilirubin.
MedLine Citation:
PMID:  17508911     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aims of the present study were to assess whether sustained HO-1 expression could moderate or prevent diabetes in an animal model of the disease and, if so, to examine the possible mechanisms involved. Our results showed that HO-1 expression and HO activity were upregulated in the pancreas of non-obese diabetic (NOD) mice by the weekly administration of cobalt protoporphyrin (CoPP). Blood glucose levels in CoPPtreated mice decreased to normal, but continuously increased in untreated controls. Beta-cell numbers were preserved in the islets of CoPP-treated mice, whereas no beta cells were found in untreated diabetic mice. The number of CD11c(+) dendritic cells was significantly decreased in the pancreas of CoPP-treated NOD mice, but this effect was reversed by the inhibition of HO activity. Increased levels of HO-1 produced a new pancreatic phenotype, as reflected by increases in phosphorylated AKT, BcL-xL and RSK levels, and decreases in O(2)- and 3-NT levels. These novel findings provide a link between the increase in HO-1 activity, with its concurrent enhanced production of carbon monoxide (CO) and bilirubin, a decrease in infiltrated CD11c(+) dendritic cells and an increase in anti-apoptotic proteins, including RSK and BcL-xL, in the interdiction of the diabetic state.
Authors:
Ming Li; Stephen Peterson; Daniel Husney; Muneo Inaba; Kequan Guo; Eri Terada; Toshisuke Morita; Kiran Patil; Attallah Kappas; Susumu Ikehara; Nader G Abraham
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  9     ISSN:  1523-0864     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-05-18     Completed Date:  2007-09-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  855-63     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD11 / metabolism
Bilirubin / metabolism*,  physiology
Blood Glucose / metabolism
Blotting, Western
Carbon Monoxide / metabolism*,  physiology
Dendritic Cells / metabolism
Diabetes Mellitus, Type 1 / drug therapy,  metabolism*,  pathology
Enzyme Activation / drug effects
Female
Glucagon / metabolism
Heme / metabolism
Heme Oxygenase (Decyclizing) / metabolism*
Heme Oxygenase-1 / metabolism
Immunohistochemistry
Insulin / metabolism
Insulin-Secreting Cells / metabolism
Mice
Mice, Inbred NOD
NADPH Oxidase / metabolism
Pancreas / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Protoporphyrins / pharmacology
bcl-X Protein / metabolism
Grant Support
ID/Acronym/Agency:
DK068134/DK/NIDDK NIH HHS; HL34300/HL/NHLBI NIH HHS; HL55601/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD11; 0/Blood Glucose; 0/Protoporphyrins; 0/bcl-X Protein; 11061-68-0/Insulin; 14325-03-2/cobaltiprotoporphyrin; 14875-96-8/Heme; 630-08-0/Carbon Monoxide; 635-65-4/Bilirubin; 9007-92-5/Glucagon; EC 1.14.99.3/Heme Oxygenase (Decyclizing); EC 1.14.99.3/Heme Oxygenase-1; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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


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