ArrayExpress Uploaderarrayexpress_sidmouse548006New insulin-producing pancreatic beta-cells are formed primarily by self-replication during adult life. To identify small molecules that...E-GEOD-12802/profile/8773/arrayexpressuploader016beta cellcellinsulinproteinDec.12, 2014FalseE-GEOD-12802_A-AFFY-45transcription-profiling-of-mouse-to-identify-smallTranscription profiling of mouse to identify small molecules which induce pancreatic beta-cell expansionNov.10, 2014New 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. Experiment Overall Design: compound treatment and time coursehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-12802http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-12802/samples/