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AuthorGul, Sarahdc.contributor.author
Date of accession2016-03-15T10:40:30Zdc.date.accessioned
Available in OPARU since2016-03-15T10:40:30Zdc.date.available
Year of creation2014dc.date.created
AbstractIn the present study we demonstrate that constitutive activation of FoxO3 results in impaired glucose and lipid metabolism in transgenic mice. FoxO3 activation resulted in impaired glucose tolerance due to upregulation of gluconeogenic target genes followed by hyperinsulinemia and impaired insulin sensitivity. Moreover expression of constitutively active FoxO3 results in activation of catabolic pathways including glycogenolysis and lipid catabolic pathways in the liver. On the other hand FoxO3 inhibits lipid synthesis pathways. Consistently our gene expression analysis has identified several genes important for regulation of glucose and lipid catabolic pathways as reported in type 2 diabetes conditions. However the disease progression in transgenic mice resulted in hypoglycemia might be as a consequence of beginning of liver failure, hyperinsulinemia and pancreatic hyperplasia. Strikingly the administration of metformin rapidly and completely normalizes glucose, insulin as well as lipid metabolism in mice expressing constitutively active FoxO3 (Figure 42). Our findings identify FoxO3 as a critical metabolic regulator and a potential hepatic target of metformin. Taken together the results obtained from constitutive activation of FoxO3 in the liver imply that dysbalanced FoxO3 activity in the liver augments insulin resistance and type 2 diabetes. Therefore tight regulation of FoxO3 activity would be very crucial and agents controlling hepatic FoxO3 system may represent therapeutic tools to prevent type 2 diabetes.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (ohne Print-On-Demand)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_opod_v1dc.rights.uri
KeywordG6PCdc.subject
KeywordPDK4dc.subject
KeywordPEPCKdc.subject
KeywordT2Ddc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHDiabetes mellitusdc.subject.mesh
MeSHFoxO3 protein, mousedc.subject.mesh
MeSHGluconeogenesisdc.subject.mesh
MeSHHypoglycemia; Physiopathologydc.subject.mesh
TitleFunctional analysis of hepatic FOXO3 signalling in glucose and lipid metabolismdc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-3289dc.identifier.doi
PPN787551872dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-90205dc.identifier.urn
GNDForkhead-Gendc.subject.gnd
GNDGluconeogenesedc.subject.gnd
GNDLeberstoffwechseldc.subject.gnd
GNDTyp 2dc.subject.gnd
FacultyFakultät für Naturwissenschaftenuulm.affiliationGeneral
Date of activation2014-05-30T09:26:21Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionW: W-H 13.649uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS-ID9020uulm.vtsID
CategoryPublikationenuulm.category
University Bibliographyjauulm.unibibliographie


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