Source:http://linkedlifedata.com/resource/pubmed/id/11672459
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2001-10-23
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pubmed:abstractText |
To test the hypothesis that changes in the expression of the glucocorticoid receptor (GCR) and the beta(2)-adrenoceptor (beta(2)-AR) contribute significantly to the abnormal glucose metabolism in skeletal muscle from patients with Type II diabetes, we have examined (1) the levels of total GCR (alpha+beta isoforms), the alpha/alpha 2 isoform of GCR and beta(2)-AR mRNAs in skeletal muscle from insulin-resistant patients with Type II diabetes (n=10) and healthy controls (n=15), and (2) the effects of 8 weeks of intensive treatment on the whole-body glucose disposal rate and on total GCR, alpha/alpha 2 GCR and beta(2)-AR mRNA levels in diabetic patients. The total glucose disposal rate was measured by the euglycaemic hyperinsulinaemic (2 m-units x min(-1) x kg(-1)) clamp technique, and mRNA levels were assessed by reverse transcriptase-PCR and HPLC for separation of standard and unknown and quantification. Mean levels of total GCR and alpha/alpha 2 GCR mRNAs were increased in patients with Type II diabetes when compared with control subjects [total GCR, 2.06+/-0.30 and 1.47+/-0.10 amol/microg of total RNA respectively (P=0.09); alpha/alpha 2 GCR mRNA, 1.69+/-0.31 and 0.92+/-0.09 amol/microg of total RNA respectively (P=0.02)], whereas mRNA levels of the beta isoform of GCR (total GCR minus alpha/alpha 2 GCR) were decreased (P=0.006). beta(2)-AR mRNA levels were comparable in diabetic patients and control subjects (0.53+/-0.05 and 0.45+/-0.02 amol/microg of total RNA respectively; P=0.2). Intensive treatment for 8 weeks was associated with improved glycaemic control (P=0.019), and during the clamp a 75% (P=0.001) increase in the whole-body insulin-stimulated glucose disposal rate was demonstrated. Total GCR (P=0.005), alpha/alpha 2 GCR (P=0.005) and beta(2)-AR (P=0.03) mRNA levels all decreased significantly after intensive insulin treatment. A close correlation was found between increments in glucose uptake during intensive treatment and decrements in skeletal muscle total GCR mRNA (r=0.95, P<0.001; multiple regression analysis), and between glucose uptake and alpha/alpha 2 GCR m RNA levels (r=0.88, P<0.001; simple correlation). In conclusion, the abnormal regulation of GCR mRNA is likely to play a significant role in the insulin resistance observed in obese patients with Type II diabetes.
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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/Gliclazide,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0143-5221
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
533-40
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11672459-Adult,
pubmed-meshheading:11672459-Aged,
pubmed-meshheading:11672459-Case-Control Studies,
pubmed-meshheading:11672459-Chromatography, High Pressure Liquid,
pubmed-meshheading:11672459-Diabetes Mellitus, Type 2,
pubmed-meshheading:11672459-Female,
pubmed-meshheading:11672459-Gliclazide,
pubmed-meshheading:11672459-Glucose Clamp Technique,
pubmed-meshheading:11672459-Humans,
pubmed-meshheading:11672459-Hypoglycemic Agents,
pubmed-meshheading:11672459-Insulin,
pubmed-meshheading:11672459-Insulin Resistance,
pubmed-meshheading:11672459-Least-Squares Analysis,
pubmed-meshheading:11672459-Linear Models,
pubmed-meshheading:11672459-Male,
pubmed-meshheading:11672459-Middle Aged,
pubmed-meshheading:11672459-Muscle, Skeletal,
pubmed-meshheading:11672459-RNA, Messenger,
pubmed-meshheading:11672459-Receptors, Glucocorticoid,
pubmed-meshheading:11672459-Regression Analysis,
pubmed-meshheading:11672459-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11672459-Statistics, Nonparametric
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pubmed:year |
2001
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pubmed:articleTitle |
Increments in insulin sensitivity during intensive treatment are closely correlated with decrements in glucocorticoid receptor mRNA in skeletal muscle from patients with Type II diabetes.
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pubmed:affiliation |
Division of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, Denmark. heve@herlevhosp.kbhamt.dk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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