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Article: Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: Roles of MAPKerk and MAPKp38

TitleRegulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: Roles of MAPKerk and MAPKp38
Authors
Issue Date2003
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2003, v. 52 n. 5, p. 1073-1080 How to Cite?
AbstractMicrosomal triglyceride transfer protein (MTP) is rate limiting for the assembly and secretion of apolipoprotein B-containing lipoproteins. Elevated hepatic MTP mRNA level, presumably as a result of impaired insulin signaling, has been implicated in the pathophysiology of dyslipidemia associated with insulin resistance/type 2 diabetes. In this study, we showed that insulin decreases MTP mRNA level mainly through transcriptional regulation in HepG2 cells. We further characterized the corresponding signal transduction pathway, using chemical inhibitors and constitutively active and dominant negative forms of regulatory enzymes. We demonstrated that insulin inhibits MTP gene transcription through MAPKerk cascade but not through the PI 3-kinase pathway. Activation of ras through farnesylation is not a prerequisite for the inhibition. In addition, cellular MAPKerk and MAPKp38 activities play a counterbalancing role in regulating the MTP gene transcription. These complex regulations may represent a means to fine-tuning MTP gene transcription in response to a diverse set of environmental stimuli and may have important implications for the onset and development of diabetes-associated dyslipidemia.
Persistent Identifierhttp://hdl.handle.net/10722/167844
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAu, WSen_US
dc.contributor.authorKung, HFen_US
dc.contributor.authorLin, MCen_US
dc.date.accessioned2012-10-08T03:12:09Z-
dc.date.available2012-10-08T03:12:09Z-
dc.date.issued2003en_US
dc.identifier.citationDiabetes, 2003, v. 52 n. 5, p. 1073-1080en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://hdl.handle.net/10722/167844-
dc.description.abstractMicrosomal triglyceride transfer protein (MTP) is rate limiting for the assembly and secretion of apolipoprotein B-containing lipoproteins. Elevated hepatic MTP mRNA level, presumably as a result of impaired insulin signaling, has been implicated in the pathophysiology of dyslipidemia associated with insulin resistance/type 2 diabetes. In this study, we showed that insulin decreases MTP mRNA level mainly through transcriptional regulation in HepG2 cells. We further characterized the corresponding signal transduction pathway, using chemical inhibitors and constitutively active and dominant negative forms of regulatory enzymes. We demonstrated that insulin inhibits MTP gene transcription through MAPKerk cascade but not through the PI 3-kinase pathway. Activation of ras through farnesylation is not a prerequisite for the inhibition. In addition, cellular MAPKerk and MAPKp38 activities play a counterbalancing role in regulating the MTP gene transcription. These complex regulations may represent a means to fine-tuning MTP gene transcription in response to a diverse set of environmental stimuli and may have important implications for the onset and development of diabetes-associated dyslipidemia.en_US
dc.languageengen_US
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_US
dc.relation.ispartofDiabetesen_US
dc.subject.meshCarcinoma, Hepatocellularen_US
dc.subject.meshCarrier Proteins - Drug Effects - Geneticsen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshHumansen_US
dc.subject.meshInsulin - Pharmacologyen_US
dc.subject.meshKineticsen_US
dc.subject.meshLiver Neoplasmsen_US
dc.subject.meshMicrosomes - Metabolismen_US
dc.subject.meshMitogen-Activated Protein Kinases - Metabolismen_US
dc.subject.meshPromoter Regions, Genetic - Drug Effectsen_US
dc.subject.meshRna, Messenger - Geneticsen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshP38 Mitogen-Activated Protein Kinasesen_US
dc.titleRegulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: Roles of MAPKerk and MAPKp38en_US
dc.typeArticleen_US
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MC=rp00746en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.2337/diabetes.52.5.1073en_US
dc.identifier.pmid12716735-
dc.identifier.scopuseid_2-s2.0-0242516072en_US
dc.identifier.hkuros79191-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0242516072&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume52en_US
dc.identifier.issue5en_US
dc.identifier.spage1073en_US
dc.identifier.epage1080en_US
dc.identifier.isiWOS:000182623500003-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridAu, WS=7202383097en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US
dc.identifier.scopusauthoridLin, MC=7404816359en_US
dc.identifier.citeulike5709368-

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