Characterising hyperinsulinemia-induced insulin resistance in human skeletal muscle cells

in Journal of Molecular Endocrinology
Authors:
Mark C Turner School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK
University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, UK

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Neil R W Martin School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK

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Darren J Player Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London, UK

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Richard A Ferguson School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK

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Patrick Wheeler School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK
University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, UK

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Charlotte J Green Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, UK

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Elizabeth C Akam School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK

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Mark P Lewis School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK
University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, UK

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Correspondence should be addressed to M C Turner: mark.turner@coventry.ac.uk

†(M C Turner is now at Centre for Sport, Exercise and Life Sciences, Faculty of Health and Life Sciences, Coventry University, Coventry, UK)

DOI:
https://doi.org/10.1530/JME-19-0169
Volume/Issue:
Volume 64: Issue 3
Article Type:
Research Article
Page Range:
125–132
Online Publication Date:
Apr 2020
Copyright:
© 2020 Society for Endocrinology 2020
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Hyperinsulinaemia 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 hyperinsulinaemia-induced insulin resistance. Differentiated HMDCs from healthy human donors were cultured with or without insulin (100 nM) for 3 days followed by an acute insulin stimulation. HMDCs 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 hyperinsulinaemia-induced insulin resistance in HMDCs.

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Online ISSN:
1479-6813
Print ISSN:
0952-5041
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
8
Article Type:
Research Article
Received Date:
20 Dec 2019
Accepted Date:
10 Jan 2020
Print Publication Date:
01 Apr 2020
Online Publication Date:
Apr 2020
Keywords:
hyperinsulinaemia; insulin resistance; diabetes mellitus; primary skeletal muscle cells

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