File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Insulin in UW solution exacerbates hepatic ischemia/reperfusion injury by energy depletion through the IRS-2/SREBP-1c pathway

TitleInsulin in UW solution exacerbates hepatic ischemia/reperfusion injury by energy depletion through the IRS-2/SREBP-1c pathway
Authors
Issue Date2004
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jtoc/106570021
Citation
Liver Transplantation, 2004, v. 10 n. 9, p. 1173-1182 How to Cite?
AbstractIschemia/reperfusion (I/R) injury is related to tissue graft energy status. Insulin, which is currently used in the University of Wisconsin (UW) preservation solution with insulin (UWI), is an anabolic hormone and was shown to exacerbate the hepatic I/R injury in our previous study. In this study, the energy status and regulation of metabolism genes by insulin were investigated in liver grafts preserved by UW solution. Insulin could significantly decrease adenosine triphosphate (ATP) level after 3 hours of preservation, as well as total adenine nucleotides (TANs) and energy charge (EC) levels. Energy regeneration deteriorated in the grafts preserved by insulin in terms of ATP and EC levels at 24 hours after transplantation. The insulin signal was transduced through the insulin receptor substrate-2 (IRS-2) pathway and the activity of IRS-2 was decreased gradually at the messenger ribonucleic acid (mRNA) level during cold preservation. Downstream targeting genes such as sterol regulatory element-binding protein-1c (SREBP-1c), glucokinase (GKC), and fatty acid synthase (FAS) genes, as well as phospho-glycogen synthase kinase-3β (GSK-3β) were activated and they showed the similar expression profiles during cold preservation. Lipoprotein metabolism was accelerated by insulin through upregulation of the activity of apolipoprotein C-III (Apo C-III) during cold preservation. The insulin-like growth factor-binding protein-1 pathway was inhibited during cold preservation. In conclusion, insulin in UW solution exacerbates hepatic I/R injury by energy depletion as the graft maintains its anabolic activity. The key enzyme activities of the energy-consuming process of glycogen and fatty acid synthesis as well as lipoprotein metabolism were accelerated by insulin through the IRS-2/SREBP-1c pathway. Copyright © 2004 by the American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/148568
ISSN
2015 Impact Factor: 3.951
2015 SCImago Journal Rankings: 1.763
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, XLen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorNg, KTen_HK
dc.contributor.authorLee, TKen_HK
dc.contributor.authorLo, CMen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2012-05-29T06:13:47Z-
dc.date.available2012-05-29T06:13:47Z-
dc.date.issued2004en_HK
dc.identifier.citationLiver Transplantation, 2004, v. 10 n. 9, p. 1173-1182en_HK
dc.identifier.issn1527-6465en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148568-
dc.description.abstractIschemia/reperfusion (I/R) injury is related to tissue graft energy status. Insulin, which is currently used in the University of Wisconsin (UW) preservation solution with insulin (UWI), is an anabolic hormone and was shown to exacerbate the hepatic I/R injury in our previous study. In this study, the energy status and regulation of metabolism genes by insulin were investigated in liver grafts preserved by UW solution. Insulin could significantly decrease adenosine triphosphate (ATP) level after 3 hours of preservation, as well as total adenine nucleotides (TANs) and energy charge (EC) levels. Energy regeneration deteriorated in the grafts preserved by insulin in terms of ATP and EC levels at 24 hours after transplantation. The insulin signal was transduced through the insulin receptor substrate-2 (IRS-2) pathway and the activity of IRS-2 was decreased gradually at the messenger ribonucleic acid (mRNA) level during cold preservation. Downstream targeting genes such as sterol regulatory element-binding protein-1c (SREBP-1c), glucokinase (GKC), and fatty acid synthase (FAS) genes, as well as phospho-glycogen synthase kinase-3β (GSK-3β) were activated and they showed the similar expression profiles during cold preservation. Lipoprotein metabolism was accelerated by insulin through upregulation of the activity of apolipoprotein C-III (Apo C-III) during cold preservation. The insulin-like growth factor-binding protein-1 pathway was inhibited during cold preservation. In conclusion, insulin in UW solution exacerbates hepatic I/R injury by energy depletion as the graft maintains its anabolic activity. The key enzyme activities of the energy-consuming process of glycogen and fatty acid synthesis as well as lipoprotein metabolism were accelerated by insulin through the IRS-2/SREBP-1c pathway. Copyright © 2004 by the American Association for the Study of Liver Diseases.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jtoc/106570021en_HK
dc.relation.ispartofLiver Transplantationen_HK
dc.subject.meshAdenosine - Chemistryen_US
dc.subject.meshAllopurinol - Chemistryen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApolipoprotein C-IIIen_US
dc.subject.meshApolipoproteins C - Metabolismen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCcaat-Enhancer-Binding Proteins - Physiologyen_US
dc.subject.meshDna-Binding Proteins - Physiologyen_US
dc.subject.meshEnergy Metabolism - Drug Effects - Physiologyen_US
dc.subject.meshGlutathione - Chemistryen_US
dc.subject.meshGlycogen Synthase Kinase 3 - Metabolismen_US
dc.subject.meshHypoglycemic Agents - Pharmacologyen_US
dc.subject.meshInsulin - Chemistry - Pharmacologyen_US
dc.subject.meshInsulin Receptor Substrate Proteinsen_US
dc.subject.meshIntracellular Signaling Peptides And Proteinsen_US
dc.subject.meshLiver Transplantation - Physiologyen_US
dc.subject.meshMaleen_US
dc.subject.meshOrgan Preservationen_US
dc.subject.meshOrgan Preservation Solutions - Chemistryen_US
dc.subject.meshPhosphoproteins - Physiologyen_US
dc.subject.meshRaffinose - Chemistryen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred Lewen_US
dc.subject.meshReperfusion Injury - Metabolism - Physiopathologyen_US
dc.subject.meshSignal Transduction - Drug Effects - Physiologyen_US
dc.subject.meshSterol Regulatory Element Binding Protein 1en_US
dc.subject.meshTranscription Factors - Physiologyen_US
dc.subject.meshUp-Regulation - Physiologyen_US
dc.titleInsulin in UW solution exacerbates hepatic ischemia/reperfusion injury by energy depletion through the IRS-2/SREBP-1c pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailNg, KT: ledodes@hku.hken_HK
dc.identifier.emailLee, TK: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityNg, KT=rp01720en_HK
dc.identifier.authorityLee, TK=rp00447en_HK
dc.identifier.authorityLo, CM=rp00412en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1002/lt.20240en_HK
dc.identifier.pmid15350011-
dc.identifier.scopuseid_2-s2.0-4544321682en_HK
dc.identifier.hkuros93975-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-4544321682&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1173en_HK
dc.identifier.epage1182en_HK
dc.identifier.isiWOS:000223674400016-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, XL=13008588500en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridNg, KT=7403178513en_HK
dc.identifier.scopusauthoridLee, TK=7501439435en_HK
dc.identifier.scopusauthoridLo, CM=7401771672en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.customcontrol.immutablesml 130620-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats