File Download
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.2337/diabetes.52.5.1073
- Scopus: eid_2-s2.0-0242516072
- PMID: 12716735
- WOS: WOS:000182623500003
- Find via
Supplementary
-
Bookmarks:
- CiteULike: 1
- Citations:
- Appears in Collections:
Article: Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: Roles of MAPKerk and MAPKp38
Title | Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: Roles of MAPKerk and MAPKp38 |
---|---|
Authors | |
Issue Date | 2003 |
Publisher | American 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? |
Abstract | Microsomal 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 Identifier | http://hdl.handle.net/10722/167844 |
ISSN | 2023 Impact Factor: 6.2 2023 SCImago Journal Rankings: 2.541 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Au, WS | en_US |
dc.contributor.author | Kung, HF | en_US |
dc.contributor.author | Lin, MC | en_US |
dc.date.accessioned | 2012-10-08T03:12:09Z | - |
dc.date.available | 2012-10-08T03:12:09Z | - |
dc.date.issued | 2003 | en_US |
dc.identifier.citation | Diabetes, 2003, v. 52 n. 5, p. 1073-1080 | en_US |
dc.identifier.issn | 0012-1797 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/167844 | - |
dc.description.abstract | Microsomal 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.language | eng | en_US |
dc.publisher | American Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/ | en_US |
dc.relation.ispartof | Diabetes | en_US |
dc.subject.mesh | Carcinoma, Hepatocellular | en_US |
dc.subject.mesh | Carrier Proteins - Drug Effects - Genetics | en_US |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Insulin - Pharmacology | en_US |
dc.subject.mesh | Kinetics | en_US |
dc.subject.mesh | Liver Neoplasms | en_US |
dc.subject.mesh | Microsomes - Metabolism | en_US |
dc.subject.mesh | Mitogen-Activated Protein Kinases - Metabolism | en_US |
dc.subject.mesh | Promoter Regions, Genetic - Drug Effects | en_US |
dc.subject.mesh | Rna, Messenger - Genetics | en_US |
dc.subject.mesh | Signal Transduction | en_US |
dc.subject.mesh | Transcription, Genetic | en_US |
dc.subject.mesh | Tumor Cells, Cultured | en_US |
dc.subject.mesh | P38 Mitogen-Activated Protein Kinases | en_US |
dc.title | Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: Roles of MAPKerk and MAPKp38 | en_US |
dc.type | Article | en_US |
dc.identifier.email | Lin, MC:mcllin@hkucc.hku.hk | en_US |
dc.identifier.authority | Lin, MC=rp00746 | en_US |
dc.description.nature | link_to_OA_fulltext | en_US |
dc.identifier.doi | 10.2337/diabetes.52.5.1073 | en_US |
dc.identifier.pmid | 12716735 | - |
dc.identifier.scopus | eid_2-s2.0-0242516072 | en_US |
dc.identifier.hkuros | 79191 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0242516072&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 52 | en_US |
dc.identifier.issue | 5 | en_US |
dc.identifier.spage | 1073 | en_US |
dc.identifier.epage | 1080 | en_US |
dc.identifier.isi | WOS:000182623500003 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Au, WS=7202383097 | en_US |
dc.identifier.scopusauthorid | Kung, HF=7402514190 | en_US |
dc.identifier.scopusauthorid | Lin, MC=7404816359 | en_US |
dc.identifier.citeulike | 5709368 | - |
dc.identifier.issnl | 0012-1797 | - |