Turner (JME ACCEPTED) - Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells_.pdf (1.06 MB)
Download fileCharacterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells
journal contribution
posted on 2021-01-01, 00:33 authored by Mark Turner, Neil MartinNeil Martin, Darren James Player, Richard FergusonRichard Ferguson, Patrick WheelerPatrick Wheeler, Charlotte JZ Green, Liz AkamLiz Akam, Mark LewisMark LewisHyperinsulinemia potentially contributes to insulin resistance in metabolic tissues, such as skeletal muscle. The purpose of these experiments was to characterise glucose uptake, insulin signalling and relevant gene expression in primary human skeletal muscle derived cells (HMDCs), in response to prolonged insulin exposure (PIE) as a model of hyperinsulinemia induced insulin resistance. Differentiated HMDCs from healthy human donors, were cultured with or without insulin (100nM) for three days followed by an acute insulin stimulation. HMDC’s exposed to PIE were characterised by impaired insulin stimulated glucose uptake, blunted IRS-1 phosphorylation (Tyr612) and Akt (Ser473) phosphorylation in response to an acute insulin stimulation. Glucose transporter 1 (GLUT1), but not GLUT4, mRNA and protein increased following PIE. The mRNA expression of metabolic (PDK4) and inflammatory markers (TNF-α) was reduced by PIE but did not change lipid (SREBP1 and CD36) or mitochondrial (UCP3) markers. These experiments provide further characterisation of the effects of PIE as a model of hyperinsulinemia induced insulin resistance in HMDCs.
Funding
National Institute for Health Research (NIHR) Leicester Biomedical Research Centre
History
School
- Sport, Exercise and Health Sciences
Published in
Journal of Molecular EndocrinologyVolume
64Issue
3Pages
125 - 132Publisher
Bioscientifica LtdVersion
- AM (Accepted Manuscript)
Rights holder
© Society for EndocrinologyPublisher statement
Disclaimer: this is not the definitive version of record of this article. This manuscript has been accepted for publication in Journal of Molecular Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. The definitive version is available at https://doi.org/10.1530/jme-19-0169 2020.Acceptance date
2020-01-10Publication date
2020-04-01ISSN
0952-5041eISSN
1479-6813Publisher version
Language
- en