![]() ![]() ![]() To enrich for causality, we refined this network by focussing on negatively associated, genetically regulated proteins, resulting in a 76-protein fingerprint of insulin resistance. Linear modelling identified 553 proteins that associated with whole-body insulin sensitivity (Matsuda Index) including regulators of endocytosis and muscle proteostasis. We leveraged this variance to explore skeletal muscle’s contribution to whole-body insulin action through metabolic phenotyping and skeletal muscle proteomics of 215 DOz mice. “Diversity Outbred in Australia (DOz)” is a population of genetically unique mice with profound metabolic heterogeneity. Systems genetics has begun to tackle the complexity of insulin resistance by capitalising on computational advances to study high-diversity populations. ![]()
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