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Multi-dimensional Transcriptional Remodeling by Physiological Insulin In Vivo.
Authors Batista TM, Garcia-Martin R, Cai W, Konishi M, O'Neill BT, Sakaguchi M, Kim JH,
Jung DY, Kim JK, Kahn CR
Submitted By Submitted Externally on 4/15/2019
Status Published
Journal Cell reports
Year 2019
Date Published 3/1/2019
Volume : Pages 26 : 3429 - 3443.e3
PubMed Reference 30893613
Abstract 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.


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