Document Detail


Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes.
MedLine Citation:
PMID:  16537919     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase. PTEN inhibits the action of phosphatidylinositol-3-kinase and reduces the levels of phosphatidylinositol triphosphate, a crucial second messenger for cell proliferation and survival, as well as insulin signaling. In this study, we deleted Pten specifically in the insulin producing beta cells during murine pancreatic development. Pten deletion leads to increased cell proliferation and decreased cell death, without significant alteration of beta-cell differentiation. Consequently, the mutant pancreas generates more and larger islets, with a significant increase in total beta-cell mass. PTEN loss also protects animals from developing streptozotocin-induced diabetes. Our data demonstrate that PTEN loss in beta cells is not tumorigenic but beneficial. This suggests that modulating the PTEN-controlled signaling pathway is a potential approach for beta-cell protection and regeneration therapies.
Authors:
Bangyan L Stiles; Christine Kuralwalla-Martinez; Wei Guo; Caroline Gregorian; Ying Wang; Jide Tian; Mark A Magnuson; Hong Wu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  26     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-15     Completed Date:  2006-04-24     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2772-81     Citation Subset:  IM    
Affiliation:
Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California 90095, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death
Cell Proliferation
Diabetes Mellitus, Experimental / chemically induced*,  pathology
Drug Resistance*
Gene Deletion*
Glucose / metabolism
Homeostasis
Insulin-Secreting Cells / cytology*,  drug effects*,  metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Mutant Strains
Organ Size
Oxidative Stress / drug effects
PTEN Phosphohydrolase / deficiency*,  genetics*,  metabolism
Streptozocin / pharmacology
Grant Support
ID/Acronym/Agency:
R01 CA107166/CA/NCI NIH HHS; UO1 CA84128-06/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
18883-66-4/Streptozocin; 50-99-7/Glucose; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase
Comments/Corrections

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


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