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Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

Turner, MC; Martin, NRW; Player, DJ; Ferguson, RA; Wheeler, P; Green, CJZ; Akam, EC; (2020) Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells. Journal of Molecular Endocrinology , 64 (3) pp. 125-132. 10.1530/JME-19-0169. Green open access

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Abstract

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.

Type: Article
Title: Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1530/JME-19-0169
Publisher version: https://doi.org/10.1530/JME-19-0169
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: hyperinsulinaemia; insulin resistance; diabetes mellitus; primary skeletal muscle cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
URI: https://discovery.ucl.ac.uk/id/eprint/10090844
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