| Identification of small-molecule inducers of pancreatic beta-cell expansion. | |
| | |
MedLine Citation:
|
PMID: 19164755 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
To identify small molecules that can induce beta-cell replication, a large chemical library was screened for proliferation of growth-arrested, reversibly immortalized mouse beta cells by using an automated high-throughput screening platform. A number of structurally diverse, active compounds were identified, including phorbol esters, which likely act through protein kinase C, and a group of thiophene-pyrimidines that stimulate beta-cell proliferation by activating the Wnt signaling pathway. A group of dihydropyridine (DHP) derivatives was also shown to reversibly induce beta-cell replication in vitro by activating L-type calcium channels (LTCCs). Our data suggest that the LTCC agonist 2a affects the expression of genes involved in cell cycle progression and cellular proliferation. Furthermore, treatment of beta cells with both LTCC agonist 2a and the Glp-1 receptor agonist Exendin-4 showed an additive effect on beta-cell replication. The identification of small molecules that induce beta-cell proliferation suggests that it may be possible to reversibly expand other quiescent cells to overcome deficits associated with degenerative and/or autoimmune diseases. |
| | |
Authors:
|
Weidong Wang; John R Walker; Xia Wang; Matthew S Tremblay; Jae Wook Lee; Xu Wu; Peter G Schultz |
Related Documents
:
|
16368785 - Imaging pancreatic beta-cells in the intact pancreas. 15031675 - Methyl-beta-cyclodextrin inhibits cell growth and cell cycle arrest via a prostaglandin... 20484465 - Genistein induces pancreatic beta-cell proliferation through activation of multiple sig... 10537065 - Proprotein convertase activity contributes to the processing of the alzheimer's beta-am... 525625 - Cyclic changes in ciliation, secretion and cell height of the oviductal epithelium in w... 10557185 - Enhanced efficacy of the combination of all-trans-retinoic acid and gamma-interferon in... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-22 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2009 Feb |
Date Detail:
|
Created Date: 2009-02-04 Completed Date: 2009-02-27 Revised Date: 2013-03-19 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 1427-32 Citation Subset: IM |
Affiliation:
|
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
GEO/GSE12802 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Calcium Channel Agonists / pharmacology* Calcium Channels, L-Type / drug effects Cell Line, Transformed Cell Proliferation / drug effects* Dihydropyridines / pharmacology Islets of Langerhans / cytology, drug effects*, metabolism Mice Oligonucleotide Array Sequence Analysis Peptides / pharmacology Receptors, Glucagon / agonists Reverse Transcriptase Polymerase Chain Reaction Venoms / pharmacology Wnt Proteins / agonists |
| Chemical | |
Reg. No./Substance:
|
0/Calcium Channel Agonists; 0/Calcium Channels, L-Type; 0/Dihydropyridines; 0/Peptides; 0/Receptors, Glucagon; 0/Venoms; 0/Wnt Proteins; 0/glucagon-like peptide-1 receptor; 141732-76-5/exenatide |
| Comments/Corrections | |
Erratum In:
|
Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7264 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The peopling of the Pacific from a bacterial perspective.
Next Document: Source modeling sleep slow waves.