Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes
Cellular and Molecular Physiology | Digestive System | Endocrinology | Genetic Phenomena | Hormones, Hormone Substitutes, and Hormone Antagonists | Lipids
Regulation of gene expression is an important aspect of insulin action but in vivo is intertwined with changing levels of glucose and counter-regulatory hormones. Here we demonstrate that under euglycemic clamp conditions, physiological levels of insulin regulate interrelated networks of more than 1,000 transcripts in muscle and liver. These include expected pathways related to glucose and lipid utilization, mitochondrial function, and autophagy, as well as unexpected pathways, such as chromatin remodeling, mRNA splicing, and Notch signaling. These acutely regulated pathways extend beyond those dysregulated in mice with chronic insulin deficiency or insulin resistance and involve a broad network of transcription factors. More than 150 non-coding RNAs were regulated by insulin, many of which also responded to fasting and refeeding. Pathway analysis and RNAi knockdown revealed a role for lncRNA Gm15441 in regulating fatty acid oxidation in hepatocytes. Altogether, these changes in coding and non-coding RNAs provide an integrated transcriptional network underlying the complexity of insulin action.
diabetes, fatty acid oxidation, gene expression, insulin action, liver, mitochondria, non-coding RNAs, skeletal muscle
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Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Cell Rep. 2019 Mar 19;26(12):3429-3443.e3. doi: 10.1016/j.celrep.2019.02.081. Link to article on publisher's site
Batista, Thiago M.; Garcia-Martin, Ruben; Cai, Weikang; Konishi, Masahiro; O'Neill, Brian T.; Sakaguchi, Masaji; Kim, Jong Hun; Jung, Dae Young; Kim, Jason K.; and Kahn, C. Ronald, "Multi-dimensional Transcriptional Remodeling by Physiological Insulin In Vivo" (2019). Open Access Articles. 3788.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.