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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1997-3-5
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pubmed:abstractText |
Nitric oxide (NO) is believed to mediate the phenomenon known as endothelium-dependent relaxation (EDR). NO synthase produces NO from its precursor, arginine (ARG). We have previously demonstrated impaired EDR in diabetic blood vessels. In this study, we investigated a possible mechanism for defective EDR in experimental diabetes and whether pancreatic islet transplantation could reverse established endothelial dysfunction. Streptozotocin-induced diabetic rats were maintained for 8 or 12 weeks. NO-mediated EDR was assessed in isolated thoracic rings ex vivo. A group of untreated diabetic rats received syngeneic islet transplantation at 8 weeks of diabetes and were tested for EDR after 4 weeks of euglycemia. EDR to acetylcholine was impaired in untreated diabetic rings. Endothelium-independent relaxation to nitroglycerin was unaltered. In vitro incubation of diabetic rings with 3 mM L-ARG (but not D-ARG) improved EDR to acetylcholine in rings from 8-week but not 12-week diabetic rats. L-ARG did not alter EDR in control rings nor relaxation to nitroglycerin in control or diabetic rings. Islet transplantation at 8 weeks of diabetes normalized blood glucose, plasma arginine and total glycosylated hemoglobin while restoring normal EDR. In conclusion, a defect in substrate/supply for NO synthesis is acutely reversed by ARG supplementation at early but not at later stages of diabetes. Also, preemptive surgical intervention with islet transplantation prior to the ARG-insensitive phase is an effective strategy to reverse established endothelial dysfunction in diabetes mellitus.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0168-8227
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
31 Suppl
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
S157-62
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8864654-Animals,
pubmed-meshheading:8864654-Arginine,
pubmed-meshheading:8864654-Blood Glucose,
pubmed-meshheading:8864654-Diabetic Angiopathies,
pubmed-meshheading:8864654-Endothelium, Vascular,
pubmed-meshheading:8864654-Islets of Langerhans Transplantation,
pubmed-meshheading:8864654-Male,
pubmed-meshheading:8864654-Nitric Oxide,
pubmed-meshheading:8864654-Rats,
pubmed-meshheading:8864654-Rats, Inbred Lew,
pubmed-meshheading:8864654-Vasodilation
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pubmed:year |
1996
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pubmed:articleTitle |
Restoration of vascular endothelial function in diabetes.
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pubmed:affiliation |
Department of Transplant Surgery, Medical College of Wisconsin Froedtert Memorial Hospital, Milwaukee 53226, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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