Linked Life Data

8522056

Source:http://linkedlifedata.com/resource/pubmed/id/8522056

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-1-25
pubmed:abstractText
Dysregulation of GLUT4, the insulin-responsive glucose transporter, is associated with insulin resistance in skeletal muscle. Although skeletal muscle is the major target of insulin action, muscle GLUT4 has not been linked causally to whole-body insulin sensitivity and regulation of glucose homeostasis. To address this, we generated a line of transgenic mice that overexpresses GLUT4 in skeletal muscle. We demonstrate that restricted overexpression of GLUT4 in fast-twitch skeletal muscles of myosin light chain (MLC)-GLUT4 transgenic mice induces a 2.5-fold increase in insulin-stimulated 2-deoxyglucose uptake in transgene-overexpressing cells. Consequently, glycogen content is increased in the fast-twitch skeletal muscles under insulin action (5.75 +/- 1.02 vs. 3.24 +/- 0.26 mg/g). This indicates that insulin-stimulated glucose transport is partly rate-limiting for glycogen synthesis. At the whole-body level, insulin-stimulated glucose turnover is increased 2.5-fold in unconscious MLC-GLUT4 mice. Plasma glucose and insulin levels in MLC-GLUT4 mice are altered as a result of increased insulin action. In 2- to 3-month-old MLC-GLUT4 mice, fasting insulin levels are decreased (0.43 +/- 0.05 vs. 0.74 +/- 0.10 microgram/l), whereas normal fasting glycemia is maintained. Conversely, 7- to 9-month-old MLC-GLUT4 mice exhibit decreased fasting glycemia (5.75 +/- 0.73 vs. 8.11 +/- 0.57 mmol/l) with normal insulin levels. Fasting plasma lactate levels are elevated in both age groups (50-100%). Additionally lipid metabolism is affected by skeletal muscle GLUT4 overexpression. This is indicated by changes in plasma free fatty acid and beta-hydroxybutyrate levels. These studies underscore the importance of GLUT4 in the regulation of glucose homeostasis and its interaction with lipid metabolism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28-36
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:8522056-Animals, pubmed-meshheading:8522056-Base Sequence, pubmed-meshheading:8522056-Biological Transport, pubmed-meshheading:8522056-Blood Glucose, pubmed-meshheading:8522056-DNA Primers, pubmed-meshheading:8522056-Deoxyglucose, pubmed-meshheading:8522056-Female, pubmed-meshheading:8522056-Gene Expression, pubmed-meshheading:8522056-Glucose, pubmed-meshheading:8522056-Glucose Transporter Type 4, pubmed-meshheading:8522056-Glycogen, pubmed-meshheading:8522056-Immunoblotting, pubmed-meshheading:8522056-Insulin, pubmed-meshheading:8522056-Lipid Metabolism, pubmed-meshheading:8522056-Male, pubmed-meshheading:8522056-Mice, pubmed-meshheading:8522056-Mice, Inbred C57BL, pubmed-meshheading:8522056-Mice, Inbred CBA, pubmed-meshheading:8522056-Mice, Transgenic, pubmed-meshheading:8522056-Molecular Sequence Data, pubmed-meshheading:8522056-Monosaccharide Transport Proteins, pubmed-meshheading:8522056-Muscle, Skeletal, pubmed-meshheading:8522056-Muscle Proteins
pubmed:year
1996
pubmed:articleTitle
Enhanced insulin action due to targeted GLUT4 overexpression exclusively in muscle.
pubmed:affiliation
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't