Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-10-23
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0143-5221
pubmed:author
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
533-40
pubmed:dateRevised
2011-11-17
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
pubmed:year
2001
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.
pubmed:affiliation
Division of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, Denmark. heve@herlevhosp.kbhamt.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't