Mouse skeletal muscle and liver in response to physiological insulin

Regulation of gene expression is an important aspect of insulin’s physiological action, however, most studies rely on in vitro systems or pharmacological doses of insulin. Here, we demonstrate that under euglycemic-clamp conditions, physiological levels of insulin regulate over 1500 transcripts in muscle and 1000 transcripts in liver. These include expected pathways related to glucose and lipid utilization, mitochondrial function and autophagy in muscle, and glucose production and steroidogenesis in liver, as well as unexpected pathways, such as mRNA splicing, chromatin remodeling, and regulation of hepatocyte nuclear factors. Insulin also regulates over 100 non-coding RNAs in muscle and liver. These changes in coding and non-coding RNAs, refined by alternative splicing, provide an integrated transcriptional network underlying the complexity of insulin action in vivo.