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Genetic variation in insulin‐induced kinase signaling

dc.contributor.authorWang, Isabel Xiaorongen_US
dc.contributor.authorRamrattan, Girishen_US
dc.contributor.authorCheung, Vivian Gen_US
dc.date.accessioned2015-08-05T16:47:07Z
dc.date.available2016-08-08T16:18:38Zen
dc.date.issued2015-07en_US
dc.identifier.citationWang, Isabel Xiaorong; Ramrattan, Girish; Cheung, Vivian G (2015). "Genetic variation in insulin‐induced kinase signaling." Molecular Systems Biology (7): n/a-n/a.en_US
dc.identifier.issn1744-4292en_US
dc.identifier.issn1744-4292en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/112224
dc.description.abstractIndividual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20‐fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis‐acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance.SynopsisGenetic variants contribute to individual variation in insulin response, including kinase activation, changes in gene expression and cell growth, suggesting kinase modulators as promising therapeutics for diseases characterized by insulin resistance.Extensive individual variation is observed in insulin‐induced activation of signal transduction.The variation in signaling response is propagated downstream to influence gene expression and cell growth.There is a genetic component to the individual differences in signaling and gene expression response to insulin.Genetic variants contribute to individual variation in insulin response, including kinase activation, changes in gene expression and cell growth, suggesting kinase modulators as promising therapeutics for diseases characterized by insulin resistance.en_US
dc.publisherInternational Diabetes Federationen_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.othersignal transductionen_US
dc.subject.othertype 2 diabetesen_US
dc.subject.otherinsulin responseen_US
dc.subject.otherindividual variationen_US
dc.subject.otherDNA variantsen_US
dc.titleGenetic variation in insulin‐induced kinase signalingen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.subject.hlbtoplevelScienceen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/1/msb156250-sup-0001-EVFigs.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/2/msb156250.reviewer_comments.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/3/msb156250.pdf
dc.identifier.doi10.15252/msb.20156250en_US
dc.identifier.sourceMolecular Systems Biologyen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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