2134/11798628.v1 Mark Turner Mark Turner Neil Martin Neil Martin Darren James Player Darren James Player Richard Ferguson Richard Ferguson Patrick Wheeler Patrick Wheeler Charlotte JZ Green Charlotte JZ Green Liz Akam Liz Akam Mark Lewis Mark Lewis Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells. Loughborough University 2020 Endocrinology & Metabolism Clinical Sciences Paediatrics and Reproductive Medicine Veterinary Sciences Hyperinsulinemia Insulin resistance Diabetes Mellitus Primary skeletal muscle cells 2020-02-04 10:54:18 Journal contribution https://repository.lboro.ac.uk/articles/journal_contribution/Characterising_hyperinsulinaemia_induced_insulin_resistance_in_human_skeletal_muscle_cells_/11798628 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.