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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1991-12-26
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pubmed:abstractText |
Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half-lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from the circulation with a T1/2 alpha of 2.9 min and a T1/2 beta of 41.1 min. The central and peripheral volume of distribution was 20.7 and 19.1 ml/rat, respectively, and the metabolic clearance rate was 16.9 ml/min/kg. The kidney and liver showed the highest accumulation of tracer, and autoradiography demonstrated that 125I-rIL-1 beta was localized to the proximal tubules in the kidney and to the hepatocytes in the liver. Furthermore, grains were localized to the islets of Langerhans in the pancreas. Tracer-bound proteins corresponding to intact 125I-rIL-1 beta were found in the circulation after i.v., intraperitoneal (i.p.) and subcutaneous (s.c.) injections, as demonstrated by high performance size exclusion chromatography, trichloracetic acid precipitation and SDS-PAGE until 5 h after tracer injection. Pre-treatment with 'cold' rIL-1 beta enhanced degradation of a subsequent injection of tracer. The route of administration was of importance for the biological effects of rIL-1 beta, as demonstrated by a reduced food intake, increased rectal temperature and blood glucose after s.c. injection of rIL-1 beta compared with i.p. The present demonstration of intact rIL-1 beta in the circulation and the islets of Langerhans supports the hypothesis that systemic IL-1 beta may be involved in the initial beta-cell destruction leading to IDDM in humans.
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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 |
Nov
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pubmed:issn |
0300-9475
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
597-610
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1947795-Animals,
pubmed-meshheading:1947795-Autoradiography,
pubmed-meshheading:1947795-Half-Life,
pubmed-meshheading:1947795-Interleukin-1,
pubmed-meshheading:1947795-Iodine Radioisotopes,
pubmed-meshheading:1947795-Male,
pubmed-meshheading:1947795-Metabolic Clearance Rate,
pubmed-meshheading:1947795-Protein Binding,
pubmed-meshheading:1947795-Rats,
pubmed-meshheading:1947795-Rats, Inbred Strains,
pubmed-meshheading:1947795-Recombinant Proteins,
pubmed-meshheading:1947795-Tissue Distribution,
pubmed-meshheading:1947795-Tumor Necrosis Factor-alpha
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pubmed:year |
1991
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pubmed:articleTitle |
The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats.
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pubmed:affiliation |
Steno Memorial and Hvidøre Hospital, Gentofte, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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