Role of PKCΖ translocation in the development of type 2 diabetes in rats following continuous glucose infusion
dc.contributor.author | Zhang, Jing-fang | en_US |
dc.contributor.author | Yang, Jing-ping Ou | en_US |
dc.contributor.author | Wang, Guang-hao | en_US |
dc.contributor.author | Xia, Zhengyuan | en_US |
dc.contributor.author | Duan, Sheng Zhong | en_US |
dc.contributor.author | Wu, Yong | en_US |
dc.date.accessioned | 2010-02-02T15:31:51Z | |
dc.date.available | 2011-03-01T16:26:45Z | en_US |
dc.date.issued | 2010-01 | en_US |
dc.identifier.citation | Zhang, Jing-fang; Yang, Jing-ping Ou; Wang, Guang-hao; Xia, Zhengyuan; Duan, Sheng Zhong; Wu, Yong (2010). "Role of PKCΖ translocation in the development of type 2 diabetes in rats following continuous glucose infusion." Diabetes/Metabolism Research and Reviews 26(1): 59-70. <http://hdl.handle.net/2027.42/64921> | en_US |
dc.identifier.issn | 1520-7552 | en_US |
dc.identifier.issn | 1520-7560 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/64921 | |
dc.description.abstract | Aim 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.format.extent | 5296186 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | John Wiley & Sons, Ltd. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Diabetes and Clinical Endocrinology | en_US |
dc.title | Role of PKCΖ translocation in the development of type 2 diabetes in rats following continuous glucose infusion | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Nephrology Division, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA | en_US |
dc.contributor.affiliationother | Department of Pathophysiology, Medical College, Wuhan University, Wuhan, Hubei, China ; Medical School, Jingchu University of Technology, Jingmen, Hubei, China | en_US |
dc.contributor.affiliationother | Department of Pathophysiology, Medical College, Wuhan University, Wuhan, Hubei, China | en_US |
dc.contributor.affiliationother | Department of Pathophysiology, Medical College, Wuhan University, Wuhan, Hubei, China ; Department of Internal Medicine, The Second People's Hospital of Jingmen City, Jingmen, Hubei, China | en_US |
dc.contributor.affiliationother | Department of Anesthesiology, Research Centre of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR, China | en_US |
dc.contributor.affiliationother | Department of Biochemistry, University of California, Riverside, CA, USA ; Department of Biochemistry, University of California, 900 University Ave., Riverside, CA 92521, USA. | en_US |
dc.identifier.pmid | 20013954 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/64921/1/1056_ftp.pdf | |
dc.identifier.doi | 10.1002/dmrr.1056 | en_US |
dc.identifier.source | Diabetes/Metabolism Research and Reviews | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.