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Proteome and Phosphoproteome Dynamics in Insulin-stimulated Myotubes
Sensitivity and plasticity of insulin signalling and glucose uptake in skeletal muscle depends on determinants such as genetic variation and obesity. Here we collected muscle biopsies from lean and obese subjects and analysed the proteome and phosphoproteome dynamics in the myotubes at baseline and two time points following a low-dose insulin stimulation (0, 5, 30 min). The myotubes initially responded to insulin stimulation with increased protein abundance and phosphorylation activities in major insulin signalling agents, decreased abundance of pro-survival proteins involved in protein translation, and increased phosphorylation of proteins in mRNA processing and splicing at 5 min. After the acute response, protein abundance returned to the basal level at 30 min, while signalling events remained elevated. A novel analysis framework KSA2D to capture joint variation in the kinase abundance at 5 min and substrate phosphorylation at both 5 min and 30 min showed that key kinases with consistently increased phosphorylation of substrates in myotubes across these subjects. Despite the shared response, we also observed increased phosphorylation of substrate proteins uniquely observed in individual groups. Our data provides a rich resource for mapping phosphorylation-mediated insulin signalling landscape in human myotubes and hypothesizing the role of associated kinases.