CEACAM1: A Molecular Link Between Fat Metabolism and Insulin Clearance

 
 
 
 

CEACAM1: A Molecular Link Between Fat Metabolism and Insulin Clearance

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dc.contributor.advisor Najjar, Ph.D., Sonia en_US
dc.contributor.author Yang, Yan en_US
dc.date.accessioned 2008-07-10T16:39:16Z
dc.date.available 2008-07-10T16:39:16Z
dc.date.created 2005 en_US
dc.date.issued 2008-07-10T16:39:16Z
dc.identifier.uri http://rave.ohiolink.edu/etdc/view?acc_num=mco1115060085 en_US
dc.identifier.uri http://hdl.handle.net/2374.OX/18119
dc.description CEACAM1 is a transmembrane glycoprotein highly expressed in liver. It downregulates the mitogenic effect of insulin, and contributes to circulating insulin level by regulating hepatic insulin clearance. We have proposed that CEACAM1 exerts its effect by taking part of the insulin endocytosis complex, and have identified Shc as an adaptor between CEACAM1 and IR. In the current studies, we explored the role of Shc/CEACAM1 complex in receptor-mediated insulin endocytosis and insulin-stimulated mitogenesis. Disruption of Shc/CEACAM1 or Shc/Grb2 interaction by overexpression the SH2 domain of Shc or of Grb2, respectively, revealed that CEACAM1 binding to Shc partitions it to the endocytosis rather than mitogenesis pathways. CEACAM1-mediated partitioning of Shc may provide a highly efficient method to regulate insulin signaling. In agreement with the role of CEACAM1 in hepatic insulin clearance, LSACC1 mice with liver-specific overexpression of the dominant-negative phosphorylation-defective CEACAM1 developed hyperinsulinemia primarily due to impaired insulin clearance. Noteworthy, there is a consistent correlation between obesity and loss of function/expression of CEACAM1 in rodent models. Herein we investigated the role of CEACAM1 in fat metabolism, and observed both in vitro and in vivo that CEACAM1 mediates an acute downregulatory effect of insulin on fatty acid synthase. We performed thorough analysis on CEACAM1/FAS interaction, and identified that it requires the phosphorylation of en_US
dc.format application/pdf en_US
dc.format 167p. en_US
dc.rights unrestricted en_US
dc.rights Copyright and permissions information available at the source archive en_US
dc.title CEACAM1: A Molecular Link Between Fat Metabolism and Insulin Clearance en_US
dc.type Electronic Thesis or Dissertation en_US
dc.degree.name PhD en_US
dc.degree.level doctoral en_US
dc.degree.discipline Graduate School en_US
dc.degree.grantor University of Toledo Health Science Campus en_US
dc.contributor.publisher University of Toledo Health Science Campus / OhioLINK en_US

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