Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-4-30
pubmed:abstractText
Loss of skeletal muscle mass and function is observed in many insulin-resistant disease states such as diabetes, cancer cachexia, renal failure and ageing although the mechanisms for this remain unclear. We hypothesised that impaired insulin signalling results in reduced muscle mass and function and that this decrease in muscle mass and function is due to both increased production of atrogenes and aberrant reactive oxygen species (ROS) generation. Maximum tetanic force of the extensor digitorum longus of muscle insulin receptor knockout (MIRKO) and lox/lox control mice was measured in situ. Muscles were removed for the measurement of mass, histological examination and ROS production. Activation of insulin signalling pathways, markers of muscle atrophy and indices of protein synthesis were determined in a separate group of MIRKO and lox/lox mice 15 min following treatment with insulin. Muscles from MIRKO mice had 36% lower maximum tetanic force generation compared with muscles of lox/lox mice. Muscle fibres of MIRKO mice were significantly smaller than those of lox/lox mice with no apparent structural abnormalities. Muscles from MIRKO mice demonstrated absent phosphorylation of AKT in response to exogenous insulin along with a failure to phosphorylate ribosomal S6 compared with lox/lox mice. Atrogin-1 and MuRF1 relative mRNA expression in muscles from MIRKO mice were decreased compared with muscles from lox/lox mice following insulin treatment. There were no differences in markers of reactive oxygen species damage between muscles from MIRKO mice and lox/lox mice. These data support the hypothesis that the absence of insulin signalling contributes to reduced muscle mass and function though decreased protein synthesis rather than proteasomal atrophic pathways.
pubmed:grant
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1574-4647
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-22
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Absence of insulin signalling in skeletal muscle is associated with reduced muscle mass and function: evidence for decreased protein synthesis and not increased degradation.
pubmed:affiliation
School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural