Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

Mark C Turner; Neil Richard William Martin; Darren James Player; Richard A Ferguson; Patrick Wheeler; Charlotte J Z Green; Elizabeth Claire Akam; Mark Peter Lewis

doi:10.1530/JME-19-0169

Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

Mark C Turner, Neil Richard William Martin, Darren James Player, Richard A Ferguson, Patrick Wheeler, Charlotte J Z Green, Elizabeth Claire Akam, Mark Peter Lewis

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Abstract

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.

Original language	English
Pages (from-to)	125-132
Number of pages	8
Journal	Molecular Endocrinology
Volume	64
Issue number	3
Early online date	1 Apr 2020
DOIs	https://doi.org/10.1530/JME-19-0169
Publication status	Published - Apr 2020
Externally published	Yes

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Molecular Endocrinology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular Endocrinology, 64:3 (2020) DOI: 10.1530/JME-19-0169

© 2020, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

diabetes mellitus
hyperinsulinaemia
insulin resistance
primary skeletal muscle cells

ASJC Scopus subject areas

Molecular Biology
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1530/JME-19-0169

Post-PrintAccepted author manuscript, 1.14 MB

Cite this

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title = "Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells",

abstract = "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.",

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AU - Akam, Elizabeth Claire

AU - Lewis, Mark Peter

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N2 - 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.

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Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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Mark Turner

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Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Mark Turner

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