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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)125-132
Number of pages8
JournalMolecular Endocrinology
Volume64
Issue number3
DOIs
Publication statusE-pub ahead of print - 1 Jan 2020
Externally publishedYes

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Keywords

  • diabetes mellitus
  • hyperinsulinaemia
  • insulin resistance
  • primary skeletal muscle cells

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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