| ChREBP mediates glucose-stimulated pancreatic β-cell proliferation. | |
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MedLine Citation:
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PMID: 22586588 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glucose stimulates rodent and human β-cell replication, but the intracellular signaling mechanisms are poorly understood. Carbohydrate response element-binding protein (ChREBP) is a lipogenic glucose-sensing transcription factor with unknown functions in pancreatic β-cells. We tested the hypothesis that ChREBP is required for glucose-stimulated β-cell proliferation. The relative expression of ChREBP was determined in liver and β-cells using quantitative RT-PCR (qRT-PCR), immunoblotting, and immunohistochemistry. Loss- and gain-of-function studies were performed using small interfering RNA and genetic deletion of ChREBP and adenoviral overexpression of ChREBP in rodent and human β-cells. Proliferation was measured by 5-bromo-2'-deoxyuridine incorporation, [(3)H]thymidine incorporation, and fluorescence-activated cell sorter analysis. In addition, the expression of cell cycle regulatory genes was measured by qRT-PCR and immunoblotting. ChREBP expression was comparable with liver in mouse pancreata and in rat and human islets. Depletion of ChREBP decreased glucose-stimulated proliferation in β-cells isolated from ChREBP(-/-) mice, in INS-1-derived 832/13 cells, and in primary rat and human β-cells. Furthermore, depletion of ChREBP decreased the glucose-stimulated expression of cell cycle accelerators. Overexpression of ChREBP amplified glucose-stimulated proliferation in rat and human β-cells, with concomitant increases in cyclin gene expression. In conclusion, ChREBP mediates glucose-stimulated proliferation in pancreatic β-cells. |
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Authors:
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Mallikarjuna R Metukuri; Pili Zhang; Mahesh K Basantani; Connie Chin; Rachel E Stamateris; Laura C Alonso; Karen K Takane; Roberto Gramignoli; Stephen C Strom; Robert M O'Doherty; Andrew F Stewart; Rupangi C Vasavada; Adolfo Garcia-Ocaña; Donald K Scott |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-05-14 |
Journal Detail:
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Title: Diabetes Volume: 61 ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-24 Completed Date: 2012-10-08 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
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Languages: eng Pagination: 2004-15 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / biosynthesis, physiology* Cell Cycle Proteins / physiology Cell Proliferation / drug effects Glucose / pharmacology* Humans Insulin-Secreting Cells / drug effects*, metabolism Insulinoma / metabolism Mice Nuclear Proteins / physiology* Rats Transcription Factors / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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DK U-01 89538/DK/NIDDK NIH HHS; DK077096/DK/NIDDK NIH HHS; DK078060/DK/NIDDK NIH HHS; DKR0155023//PHS HHS; R56DK065149/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0/Cell Cycle Proteins; 0/MLXIPL protein, human; 0/Nuclear Proteins; 0/Transcription Factors; 0/Wbscr14 protein, rat; 0/carbohydrate response element binding protein, mouse; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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