Turner (JME ACCEPTED) - Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells_.pdf (1.06 MB)
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Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

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journal contribution
posted on 01.01.2021, 00:33 by Mark Turner, Neil MartinNeil Martin, Darren James Player, Richard FergusonRichard Ferguson, Patrick WheelerPatrick Wheeler, Charlotte JZ Green, Liz AkamLiz Akam, Mark LewisMark Lewis
Hyperinsulinemia 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 Endocrinology

Volume

64

Issue

3

Pages

125 - 132

Publisher

Bioscientifica Ltd

Version

AM (Accepted Manuscript)

Rights holder

© Society for Endocrinology

Publisher 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

10/01/2020

Publication date

2020-04-01

ISSN

0952-5041

eISSN

1479-6813

Language

en

Depositor

Dr Neil Martin Deposit date: 4 February 2020