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.