Source:http://linkedlifedata.com/resource/pubmed/id/15654653
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2005-1-17
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| pubmed:abstractText |
The diabetes (db/db) genotype mutation induces a hyperglycemic-hyperinsulinemic endometabolic state in C57BL/KsJ mice, manifesting a type 2 NIDDM diabetes-obesity syndrome (DOS) in this hyperphagic, leptin receptor (lf) defective model. The severity of the DOS induced by the single gene, homozygous-recessive mutation may be therapeutically moderated by gonadal steroids and pre-steroidal metabolites. The current studies define the estradiol (E2)-modulated phenotypic, systemic, cytochemical, and cellular metabolic responses to db/db mutation expression as compared to littermate control (+/?) indices. The db/db mutation induced dramatic age- and DOS severity-related increases in body weights, blood glucose, and serum insulin concentrations relative to +/? indices between 4-week-old (i.e., initial onset stage of DOS phenotype) and 16-week-old (i.e., chronic stage of DOS) groups. Chronic, low-dose (0.1 microg/3.5 days) E2 treatment (E2-HRx) significantly reduced the obesity mass and blood glucose levels of db/db mutants relative to oil-HRx groups. Similarly, E2-HRx maintained pancreatic glucose utilization rates and pancreatic tissue weights in db/db mutants to near +/? indices. Concurrent amelioration of db/db-enhanced pancreatic lipogenesis and islet hypercytolipidemia occurred following E2-HRx. Pancreatic islet lipo-deposition was markedly reduced in db/db mutants following E2-HRx, and the restoration of islet size and cellular insulin concentrations correlated with beta-cell cytoplasmic regranulation of insulin secretory vesicles. In chronic E2-HRx db/db groups, autoradiographic localization of (3)H-E2 was demonstrated in the nuclear compartments of regranulated, nonhypertrophic islet cell populations, including insulin-containing beta-cells. In chronic E2-HRx db/db mutants, beta-cell insulin granulation was prominent in mildly hypertrophic pancreatic islets, with cytodistribution patterns and concentrations comparable to normal +/? indices. In contrast, E2-HRx maintained the systemic hyperinsulinemia characteristic of oil-HRx db/db mutants. The results of these studies indicate that the severity of the type 2 NIDDM endometabolic syndrome induced by the db/db genotypic mutation may be influenced by E2-HRx, including reduction of the islet hypercytolipidemia and hypertrophic atrophy which are indicators of impending pancreatic involution in this mutant model. The hypercytolipidemia-induced demise of beta-cell cytoarchitecture was reduced by E2-HRx, including the reestablishment of islet beta-cell cytogranulation. These data suggest that the severity of genomic db/db-mutation expression may be modified by E2-HRx, with the gonadal steroid probably acting as a nuclear-specific stimulatory transcriptional modulator of cellular glucometabolic cascades in the absence of leptin-directed homeostatic influences.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetyl-CoA Carboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0302-766X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
319
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
231-42
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:15654653-Acetyl-CoA Carboxylase,
pubmed-meshheading:15654653-Animals,
pubmed-meshheading:15654653-Atrophy,
pubmed-meshheading:15654653-Autoradiography,
pubmed-meshheading:15654653-Blood Glucose,
pubmed-meshheading:15654653-Body Weight,
pubmed-meshheading:15654653-Cell Nucleus,
pubmed-meshheading:15654653-Diabetes Mellitus, Type 2,
pubmed-meshheading:15654653-Estradiol,
pubmed-meshheading:15654653-Female,
pubmed-meshheading:15654653-Genes, Recessive,
pubmed-meshheading:15654653-Histocytochemistry,
pubmed-meshheading:15654653-Homozygote,
pubmed-meshheading:15654653-Hyperglycemia,
pubmed-meshheading:15654653-Hyperinsulinism,
pubmed-meshheading:15654653-Hyperlipidemias,
pubmed-meshheading:15654653-Injections, Subcutaneous,
pubmed-meshheading:15654653-Insulin,
pubmed-meshheading:15654653-Islets of Langerhans,
pubmed-meshheading:15654653-Mice,
pubmed-meshheading:15654653-Mice, Inbred C57BL,
pubmed-meshheading:15654653-Mice, Mutant Strains,
pubmed-meshheading:15654653-Mutation,
pubmed-meshheading:15654653-Obesity,
pubmed-meshheading:15654653-Organ Size,
pubmed-meshheading:15654653-Radioimmunoassay,
pubmed-meshheading:15654653-Time Factors,
pubmed-meshheading:15654653-Tritium
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| pubmed:year |
2005
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| pubmed:articleTitle |
Estrogenic restoration of functional pancreatic islet cytoarchitecture in diabetes (db/db) mutant C57BL/KsJ mice: relationship to estradiol localization, systemic glycemia, and persistent hyperinsulinemia.
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| pubmed:affiliation |
Division of Cell Biology and Biophysics, Schools of Biological Sciences and Medicine, University of Missouri-Kansas City, 5007 Rockhill Road, Kansas City, MO 64110, USA. garrisd@umkc.edu
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| pubmed:publicationType |
Journal Article
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