File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: APPL1 Potentiates Insulin-Mediated Inhibition of Hepatic Glucose Production and Alleviates Diabetes via Akt Activation in Mice

TitleAPPL1 Potentiates Insulin-Mediated Inhibition of Hepatic Glucose Production and Alleviates Diabetes via Akt Activation in Mice
Authors
KeywordsHUMDISEASE
SIGNALING
Issue Date2009
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cellmet
Citation
Cell Metabolism, 2009, v. 9 n. 5, p. 417-427 How to Cite?
AbstractHepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. Here we report that the endosomal adaptor protein APPL1 increases hepatic insulin sensitivity by potentiating insulin-mediated suppression of the gluconeogenic program. Insulin-stimulated activation of Akt and suppression of gluconeogenesis in hepatocytes are enhanced by APPL1 overexpression, but are attenuated by APPL1 knockdown. APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor tribble 3 (TRB3) through direct competition, thereby promoting Akt translocation to the plasma membrane and the endosomes for further activation. In db/db diabetic mice, the blockage of the augmented interaction between Akt and TRB3 by hepatic overexpression of APPL1 is accompanied by a marked attenuation of hyperglycemia and insulin resistance. These results suggest that the potentiating effects of APPL1 on insulin-stimulated suppression of hepatic glucose production are attributed to its ability in counteracting the inhibition of Akt activation by TRB3. © 2009 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59315
ISSN
2015 Impact Factor: 17.303
2015 SCImago Journal Rankings: 11.842
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 779707M
HKU 2/07C
National 973 Program of China2006CB503908
National Health and Medical Research Council of Australia
Funding Information:

This work was supported by the general research fund (HKU 779707M to AX) and collaborative research fund (HKU 2/07C) from the Research Grants Council of Hong Kong, the National 973 Program of China (2006CB503908), and the National Health and Medical Research Council of Australia (to E.W.K.).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorCheng, KKYen_HK
dc.contributor.authorIglesias, MAen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorSweeney, Gen_HK
dc.contributor.authorZhu, Wen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorKraegen, EWen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2010-05-31T03:47:34Z-
dc.date.available2010-05-31T03:47:34Z-
dc.date.issued2009en_HK
dc.identifier.citationCell Metabolism, 2009, v. 9 n. 5, p. 417-427en_HK
dc.identifier.issn1550-4131en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59315-
dc.description.abstractHepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. Here we report that the endosomal adaptor protein APPL1 increases hepatic insulin sensitivity by potentiating insulin-mediated suppression of the gluconeogenic program. Insulin-stimulated activation of Akt and suppression of gluconeogenesis in hepatocytes are enhanced by APPL1 overexpression, but are attenuated by APPL1 knockdown. APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor tribble 3 (TRB3) through direct competition, thereby promoting Akt translocation to the plasma membrane and the endosomes for further activation. In db/db diabetic mice, the blockage of the augmented interaction between Akt and TRB3 by hepatic overexpression of APPL1 is accompanied by a marked attenuation of hyperglycemia and insulin resistance. These results suggest that the potentiating effects of APPL1 on insulin-stimulated suppression of hepatic glucose production are attributed to its ability in counteracting the inhibition of Akt activation by TRB3. © 2009 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cellmeten_HK
dc.relation.ispartofCell Metabolismen_HK
dc.subjectHUMDISEASEen_HK
dc.subjectSIGNALINGen_HK
dc.subject.meshAdaptor Proteins, Signal Transducing - metabolismen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBinding, Competitiveen_HK
dc.subject.meshCarrier Proteins - metabolismen_HK
dc.subject.meshCell Cycle Proteins - metabolismen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshDiabetes Mellitus, Type 2 - enzymologyen_HK
dc.subject.meshGene Knockdown Techniquesen_HK
dc.subject.meshGluconeogenesisen_HK
dc.subject.meshGlucose - biosynthesis - metabolismen_HK
dc.subject.meshHepatocytes - enzymologyen_HK
dc.subject.meshInsulin - metabolismen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMice, Obeseen_HK
dc.subject.meshNerve Tissue Proteins - metabolismen_HK
dc.subject.meshProto-Oncogene Proteins c-akt - metabolismen_HK
dc.subject.meshRNA Interferenceen_HK
dc.subject.meshRatsen_HK
dc.subject.meshSignal Transductionen_HK
dc.titleAPPL1 Potentiates Insulin-Mediated Inhibition of Hepatic Glucose Production and Alleviates Diabetes via Akt Activation in Miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1550-4131&volume=9&spage=417&epage=427&date=2009&atitle=Appl1+Potentiates+Insulin-mediated+Inhibition+Of+Hepatic+Glucose+Production+And+Alleviates+Diabetes+Via+Akt+Activation+In+Miceen_HK
dc.identifier.emailCheng, KKY: dorncky@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityCheng, KKY=rp01672en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.cmet.2009.03.013en_HK
dc.identifier.pmid19416712-
dc.identifier.scopuseid_2-s2.0-65449161015en_HK
dc.identifier.hkuros157434en_HK
dc.identifier.hkuros158063-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65449161015&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume9en_HK
dc.identifier.issue5en_HK
dc.identifier.spage417en_HK
dc.identifier.epage427en_HK
dc.identifier.eissn1932-7420-
dc.identifier.isiWOS:000265841700006-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectAPPL1 as a novel modulator of endothelial nitric oxide production and endothelium-dependent vasodilation-
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.identifier.scopusauthoridCheng, KKY=7402997599en_HK
dc.identifier.scopusauthoridIglesias, MA=7102184942en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridSweeney, G=7102852659en_HK
dc.identifier.scopusauthoridZhu, W=7404232544en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridKraegen, EW=7006873142en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats