Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen.
Phenothiazine neuroleptics signal to the human insulin promoter as revealed by a novel high-throughput screen.
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DOI：
10.1177/1087057110372257
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发表时间：
2010-07
影响因子：
--
通讯作者：
Levine F
中科院分区：
文献类型：
--
作者：
Kiselyuk A;Farber-Katz S;Cohen T;Lee SH;Geron I;Azimi B;Heynen-Genel S;Singer O;Price J;Mercola M;Itkin-Ansari P;Levine F
A number of diabetogenic stimuli interact to influence insulin promoter activity, making it an attractive target for both mechanistic studies and therapeutic interventions. High-throughput screening (HTS) for insulin promoter modulators has the potential to reveal novel inputs into the control of that central element of the pancreatic β-cell. A cell line from human islets in which the expression of insulin and other β-cell-restricted genes are modulated by an inducible form of the bHLH transcription factor E47 was developed. This cell line, T6PNE, was adapted for HTS by transduction with a vector expressing green fluorescent protein under the control of the human insulin promoter. The resulting cell line was screened against a library of known drugs for those that increase insulin promoter activity. Members of the phenothiazine class of neuroleptics increased insulin gene expression upon short-term exposure. Chronic treatment, however, resulted in suppression of insulin promoter activity, consistent with the effect of phenothiazines observed clinically to induce diabetes in chronically treated patients. In addition to providing insights into previously unrecognized targets and mechanisms of action of phenothiazines, the novel cell line described here provides a broadly applicable platform for mining new molecular drug targets and central regulators of β-cell differentiated function.
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影响因子：
4.8
作者：
Odagiri, H;Wang, J;German, MS
通讯作者：
German, MS
DOI：
10.1530/acta.0.1160241
发表时间：
1987-10-01
期刊：
ACTA ENDOCRINOLOGICA
影响因子：
--
作者：
KRAUSZ, Y;EYLON, L;CERASI, E
通讯作者：
CERASI, E
影响因子：
14.9
作者：
Barrett T;Troup DB;Wilhite SE;Ledoux P;Rudnev D;Evangelista C;Kim IF;Soboleva A;Tomashevsky M;Marshall KA;Phillippy KH;Sherman PM;Muertter RN;Edgar R
通讯作者：
Edgar R
影响因子：
1.8
作者：
PALMER, GC;BLOSSER, JC;MANIAN, AA
通讯作者：
MANIAN, AA
影响因子：
2.7
作者：
Kutlu, Burak;Burdick, David;Baxter, David;Rasschaert, Joanne;Flamez, Daisy;Eizirik, Decio L.;Welsh, Nils;Goodman, Nathan;Hood, Leroy
通讯作者：
Hood, Leroy