Document Detail


Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass.
MedLine Citation:
PMID:  22595886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A decrease in the expression of Islet-1 (Isl-1), an islet transcription factor, has been reported in several physiological settings of reduced β-cell function. Here, we investigate whether an increased level of Isl-1 in islet cells can enhance β-cell function and/or mass. We demonstrate that transgenic mice with Isl-1 overexpression display improved glucose tolerance and enhanced insulin secretion without significant changes in β cell mass. From our microarray study, we identify approximately 135 differentially expressed genes in the islets of Isl-1 overexpressing mice that have been implicated to function in numerous biological processes including protein trafficking, metabolism and differentiation. Using real-time PCR we have confirmed upregulation of Caps2, Sec14l4, Slc2a10, P2rx7, Afamin, and Neurogenin 3 that may in part mediate the observed improved insulin secretion in Isl-1 overexpressing mice. These findings show for the first time that Isl-1 is a key factor in regulating adult β cell function in vivo, and suggest that Isl-1 elevation could be beneficial to improve glucose homeostasis.
Authors:
Jingxuan Liu; Erik R Walp; Catherine Lee May
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-01
Journal Detail:
Title:  Islets     Volume:  4     ISSN:  1938-2022     ISO Abbreviation:  Islets     Publication Date:    2012 May-Jun
Date Detail:
Created Date:  2012-07-31     Completed Date:  2013-03-08     Revised Date:  2013-06-24    
Medline Journal Info:
Nlm Unique ID:  101495366     Medline TA:  Islets     Country:  United States    
Other Details:
Languages:  eng     Pagination:  199-206     Citation Subset:  IM    
Affiliation:
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Diabetes Mellitus / metabolism,  pathology
Gene Expression Profiling
Gene Expression Regulation
Glucose / metabolism
Insulin / metabolism
Insulin-Secreting Cells / cytology,  metabolism,  physiology*
LIM-Homeodomain Proteins / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Oligonucleotide Array Sequence Analysis
RNA / chemistry,  genetics
Real-Time Polymerase Chain Reaction
Transcription Factors / metabolism*
Grant Support
ID/Acronym/Agency:
DK078606/DK/NIDDK NIH HHS; P30-DK050306/DK/NIDDK NIH HHS; P30-DK19525/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Insulin; 0/LIM-Homeodomain Proteins; 0/Transcription Factors; 0/insulin gene enhancer binding protein Isl-1; 50-99-7/Glucose; 63231-63-0/RNA
Comments/Corrections

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


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