| Adenosine signaling promotes regeneration of pancreatic β cells in vivo. | |
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MedLine Citation:
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PMID: 22608007 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Diabetes can be controlled with insulin injections, but a curative approach that restores the number of insulin-producing β cells is still needed. Using a zebrafish model of diabetes, we screened ~7,000 small molecules to identify enhancers of β cell regeneration. The compounds we identified converge on the adenosine signaling pathway and include exogenous agonists and compounds that inhibit degradation of endogenously produced adenosine. The most potent enhancer of β cell regeneration was the adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA), which, acting through the adenosine receptor A2aa, increased β cell proliferation and accelerated restoration of normoglycemia in zebrafish. Despite markedly stimulating β cell proliferation during regeneration, NECA had only a modest effect during development. The proliferative and glucose-lowering effect of NECA was confirmed in diabetic mice, suggesting an evolutionarily conserved role for adenosine in β cell regeneration. With this whole-organism screen, we identified components of the adenosine pathway that could be therapeutically targeted for the treatment of diabetes. |
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Authors:
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Olov Andersson; Bruce A Adams; Daniel Yoo; Gregory C Ellis; Philipp Gut; Ryan M Anderson; Michael S German; Didier Y R Stainier |
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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: 2012-05-17 |
Journal Detail:
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Title: Cell metabolism Volume: 15 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-06-11 Completed Date: 2012-10-02 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 885-94 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry and Biophysics, Program in Developmental and Stem Cell Biology and Program in Genetics and Human Genetics, Diabetes Center, Institute for Regeneration Medicine and Liver Center, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158, USA. olov.andersson@ki.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine
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metabolism,
physiology* Adenosine-5'-(N-ethylcarboxamide) / pharmacology*, therapeutic use Animals Blood Glucose Cell Proliferation / drug effects Cell Survival / drug effects Diabetes Mellitus, Experimental / drug therapy, pathology Drug Evaluation, Preclinical Insulin-Secreting Cells / drug effects, metabolism*, physiology Larva / drug effects Mice Pancreas / drug effects, pathology, physiology Purinergic P1 Receptor Agonists / pharmacology*, therapeutic use Receptor, Adenosine A2A / metabolism Regeneration Zebrafish Zebrafish Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK075032/DK/NIDDK NIH HHS; R01DK075032/DK/NIDDK NIH HHS; U01 DK089541/DK/NIDDK NIH HHS; U01DK089541/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Purinergic P1 Receptor Agonists; 0/Receptor, Adenosine A2A; 0/Zebrafish Proteins; 35920-39-9/Adenosine-5'-(N-ethylcarboxamide); 58-61-7/Adenosine |
| Comments/Corrections | |
Comment In:
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Dis Model Mech. 2012 Nov;5(6):709-10
[PMID:
23115198
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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