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.
Bibliographical noteNOTICE: 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/
- diabetes mellitus
- insulin resistance
- primary skeletal muscle cells
ASJC Scopus subject areas
- Molecular Biology
FingerprintDive into the research topics of 'Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells'. Together they form a unique fingerprint.
- Research Centre for Sport, Exercise and Life Sciences - Assistant Professor (Research)
Person: Teaching and Research