File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Role of PKCζ translocation in the development of type 2 diabetes in rats following continuous glucose infusion

TitleRole of PKCζ translocation in the development of type 2 diabetes in rats following continuous glucose infusion
Authors
Issue Date2010
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/10009394
Citation
Diabetes/Metabolism Research And Reviews, 2010, v. 26 n. 1, p. 59-70 How to Cite?
AbstractAim: We investigated the molecular mechanisms of hyperglycaemia-induced insulin resistance and type 2 diabetes in rats receiving a continuous glucose infusion (GI). Methods; Female Wistar rats were infused with either 2.8 mol/L glucose or saline (2 mL/h) for durations varying from 0 to 15 days. Blood samples were analysed daily to determine glucose and insulin dynamics. Subsets of animals were sacrificed and solues muscles were extracted for determination of protein expression, subcellular location, and activities of insulin-signalling proteins. Results: Rats accommodated this systemic glucose oversupply and developed insulin resistance on day 5 (normoglycaemia/ hyperinsulinaemia) and type 2 diabetes on day 15 (hyperglycaemia/ normoinsulinaemia). The effect of GI on protein kinase Cζ (PKCζ ) activity was independent of changes in phosphatidylinositol 3-kinase activity, and occurred in parallel with an increase in PDK1 activity. Activated PKCζ was mainly located in the cytosol after 5 days of GI that was coincident with the translocation of GLUT4 to the plasma membrane, and normoglycaemia. After 15 days of GI, PKCζ translocated from the cytosol to the plasma membrane with a concomitant decrease in PDK1 activity. This caused an increase in the association between PKCζ and PKB and a decrease in PDK1-PKB reactions at the plasma membrane, leading to reduced PKB activity. The activity of PKCζ per se was also compromised. The PKCζ and PKB activity reduction and the blunted insulin-stimulated GLUT4 translocation eventually led to hyperglycaemia and diabetes. Conclusion: Translocation of PKCζ may play a central role in the development of type 2 diabetes. Copyright © 2009 John Wiley & Sons, Ltd.
metadata.dc.description.urihttps://www.researchgate.net/publication/40691339_Role_of_PKCzeta_translocation_in_the_development_of_type_2_diabetes_in_rats_following_continuous_glucose_infusion
Persistent Identifierhttp://hdl.handle.net/10722/147272
ISSN
2012 Impact Factor: 2.968
2015 SCImago Journal Rankings: 1.617
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30370673
Educational Bureau of Hubei30113065
Funding Information:

We thank Herman Rhee, PhD for valuable discussion and critical review of the manuscript. This work was supported by a grant (NO. 30370673) from National Natural Science Foundation of China and a grant (NO. 30113065) from the Educational Bureau of Hubei.

References

 

DC FieldValueLanguage
dc.contributor.authorZhang, JFen_US
dc.contributor.authorYang, JPOen_US
dc.contributor.authorWang, GHen_US
dc.contributor.authorXia, Zen_US
dc.contributor.authorDuan, SZen_US
dc.contributor.authorWu, Yen_US
dc.date.accessioned2012-05-29T06:01:09Z-
dc.date.available2012-05-29T06:01:09Z-
dc.date.issued2010en_US
dc.identifier.citationDiabetes/Metabolism Research And Reviews, 2010, v. 26 n. 1, p. 59-70en_US
dc.identifier.issn1520-7552en_US
dc.identifier.urihttp://hdl.handle.net/10722/147272-
dc.description.abstractAim: We investigated the molecular mechanisms of hyperglycaemia-induced insulin resistance and type 2 diabetes in rats receiving a continuous glucose infusion (GI). Methods; Female Wistar rats were infused with either 2.8 mol/L glucose or saline (2 mL/h) for durations varying from 0 to 15 days. Blood samples were analysed daily to determine glucose and insulin dynamics. Subsets of animals were sacrificed and solues muscles were extracted for determination of protein expression, subcellular location, and activities of insulin-signalling proteins. Results: Rats accommodated this systemic glucose oversupply and developed insulin resistance on day 5 (normoglycaemia/ hyperinsulinaemia) and type 2 diabetes on day 15 (hyperglycaemia/ normoinsulinaemia). The effect of GI on protein kinase Cζ (PKCζ ) activity was independent of changes in phosphatidylinositol 3-kinase activity, and occurred in parallel with an increase in PDK1 activity. Activated PKCζ was mainly located in the cytosol after 5 days of GI that was coincident with the translocation of GLUT4 to the plasma membrane, and normoglycaemia. After 15 days of GI, PKCζ translocated from the cytosol to the plasma membrane with a concomitant decrease in PDK1 activity. This caused an increase in the association between PKCζ and PKB and a decrease in PDK1-PKB reactions at the plasma membrane, leading to reduced PKB activity. The activity of PKCζ per se was also compromised. The PKCζ and PKB activity reduction and the blunted insulin-stimulated GLUT4 translocation eventually led to hyperglycaemia and diabetes. Conclusion: Translocation of PKCζ may play a central role in the development of type 2 diabetes. Copyright © 2009 John Wiley & Sons, Ltd.en_US
dc.description.urihttps://www.researchgate.net/publication/40691339_Role_of_PKCzeta_translocation_in_the_development_of_type_2_diabetes_in_rats_following_continuous_glucose_infusion-
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/10009394en_US
dc.relation.ispartofDiabetes/Metabolism Research and Reviewsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDiabetes Mellitus, Type 2 - Enzymologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGlucose - Administration & Dosage - Pharmacologyen_US
dc.subject.meshGlucose Transporter Type 4 - Metabolismen_US
dc.subject.meshHindlimben_US
dc.subject.meshInfusions, Intravenousen_US
dc.subject.meshInsulin Resistance - Physiologyen_US
dc.subject.meshMuscle, Skeletal - Drug Effects - Enzymologyen_US
dc.subject.meshPhosphatidylinositol 3-Kinases - Metabolismen_US
dc.subject.meshProtein Kinase C - Metabolismen_US
dc.subject.meshProtein Transporten_US
dc.subject.meshProtein-Serine-Threonine Kinases - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins C-Akt - Metabolismen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Wistaren_US
dc.titleRole of PKCζ translocation in the development of type 2 diabetes in rats following continuous glucose infusionen_US
dc.typeArticleen_US
dc.identifier.emailXia, Z:zyxia@hkucc.hku.hken_US
dc.identifier.authorityXia, Z=rp00532en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/dmrr.1056en_US
dc.identifier.pmid20013954-
dc.identifier.scopuseid_2-s2.0-75449102371en_US
dc.identifier.hkuros171201-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-75449102371&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume26en_US
dc.identifier.issue1en_US
dc.identifier.spage59en_US
dc.identifier.epage70en_US
dc.identifier.isiWOS:000274609400010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.citeulike6416573-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats