Document Detail

Proteomic identification of carboxypeptidase E connects lipid-induced beta-cell apoptosis and dysfunction in type 2 diabetes.
MedLine Citation:
PMID:  19106615     Owner:  NLM     Status:  MEDLINE    
Type 2 diabetes occurs when the endocrine pancreas can no longer secrete enough insulin to maintain glucose and lipid homeostasis. This is likely due to cumulative defects in beta-cell fate and function, as well as insulin resistance. A number of recent studies, including ones from our group, have used unbiased proteomic, genomic and genetic approaches to unravel the mechanisms by which hyperlipidemia causes beta-cell apoptosis and dysfunction. It is clear from these studies and others, that there are multiple pathways by which fatty acids such as palmitate can lead to beta-cell dysfunction and death. In the present article, we highlight the role for dysfunction in the ER and secretory pathway in the toxic effects of free fatty acids. Recent work has shown that the rapid degradation of carboxypeptidase E plays a significant role in beta-cell death in response to the free fatty acid palmitate. These newly identified targets of beta-cell lipotoxicity present novel avenues for research and therapeutic intervention.
James D Johnson
Related Documents :
7645035 - Cyclosporine stimulates expression of transforming growth factor-beta in renal cells. p...
20395405 - Derepression of polycomb targets during pancreatic organogenesis allows insulin-produci...
8420395 - Effects of prolactin on alpha and beta chloride cells in the gill epithelium of the sal...
9185755 - Assessment of the role of activin a and transforming growth factor beta in the regulati...
11927285 - Complexities in the development of cyclin-dependent kinase inhibitor drugs.
22281785 - Proliferation and mrna expression of absorptive villous cell markers and mineral transp...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-04
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  8     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-22     Completed Date:  2009-02-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38-42     Citation Subset:  IM    
Laboratory of Molecular Signalling in Diabetes, Life Sciences Institute, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis / drug effects*
Carboxypeptidase H / metabolism*
Diabetes Mellitus, Type 2 / enzymology*,  pathology,  physiopathology*
Insulin-Secreting Cells / drug effects,  pathology*
Lipids / pharmacology*
Models, Biological
Palmitates / pharmacology
Reg. No./Substance:
0/Lipids; 0/Palmitates; EC H

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Identification of two independent SUMO-interacting motifs in Daxx: evolutionary conservation from Dr...
Next Document:  The p53 mRNA-Mdm2 interaction.