|
| Status |
Public on Jan 19, 2009 |
| Title |
Small molecule inducers of pancreatic beta-cell expansion |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
New insulin-producing pancreatic beta-cells are formed primarily by self-replication during adult life. 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 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 indicate 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 Ex-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.
Keywords: treatment and time course
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| |
|
| Overall design |
compound treatment and time course
|
| |
|
| Contributor(s) |
Wang W, Walker JR, Wang X, Tremblay M, Lee JW, Wu X, Schultz PG |
| Citation(s) |
19164755 |
| |
| Submission date |
Sep 16, 2008 |
| Last update date |
Feb 11, 2019 |
| Contact name |
John R Walker |
| E-mail(s) |
jwalker@gnf.org
|
| Phone |
858-812-1636
|
| Organization name |
Genomics Institute of the Novartis Research Foundation
|
| Lab |
Genetics Core
|
| Street address |
10675 John Jay Hopkins
|
| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA112755 |
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