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
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- Sport, Exercise and Health Sciences