Multi-dimensional Transcriptional Remodeling by Physiological Insulin In Vivo

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dc.contributor.authorBatista, Thiago M.
dc.contributor.authorGarcia-Martin, Ruben
dc.contributor.authorCai, Weikang
dc.contributor.authorKonishi, Masahiro
dc.contributor.authorO'Neill, Brian T.
dc.contributor.authorSakaguchi, Masaji
dc.contributor.authorKim, Jong Hun
dc.contributor.authorJung, Dae Young
dc.contributor.authorKim, Jason K
dc.contributor.authorKahn, C. Ronald
dc.contributor.departmentDepartment of Medicine, Division of Endocrinology, Metabolism, and Diabetes
dc.contributor.departmentProgram in Molecular Medicine
dc.date2022-08-11T08:09:52.000
dc.date.accessioned2022-08-23T16:47:00Z
dc.date.available2022-08-23T16:47:00Z
dc.date.issued2019-03-19
dc.date.submitted2019-05-16
dc.description.abstractRegulation 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.
dc.identifier.citation<p>Cell Rep. 2019 Mar 19;26(12):3429-3443.e3. doi: 10.1016/j.celrep.2019.02.081. <a href="https://doi.org/10.1016/j.celrep.2019.02.081">Link to article on publisher's site</a></p>
dc.identifier.contextkey14516629
dc.identifier.doi10.1016/j.celrep.2019.02.081
dc.identifier.issn2211-1247 (Electronic)
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3788
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4802&amp;context=oapubs&amp;unstamped=1
dc.identifier.pmid30893613
dc.identifier.submissionpathoapubs/3788
dc.identifier.urihttps://hdl.handle.net/20.500.14038/40991
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30893613&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright 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/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.source.issue12
dc.source.journaltitleCell reports
dc.source.pages3429-3443.e3
dc.source.volume26
dc.subjectdiabetes
dc.subjectfatty acid oxidation
dc.subjectgene expression
dc.subjectinsulin action
dc.subjectliver
dc.subjectmitochondria
dc.subjectnon-coding RNAs
dc.subjectskeletal muscle
dc.subjectCellular and Molecular Physiology
dc.subjectDigestive System
dc.subjectEndocrinology
dc.subjectGenetic Phenomena
dc.subjectHormones, Hormone Substitutes, and Hormone Antagonists
dc.subjectLipids
dc.titleMulti-dimensional Transcriptional Remodeling by Physiological Insulin In Vivo
dc.typeJournal Article
dspace.entity.typePublication
html.description.abstract<p>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.</p>
refterms.dateFOA2022-08-23T16:47:00Z
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