Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing.

Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing. Research Abstract Details 

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Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing. Abstract Text:

Weizhen Wu,Jin Shang,Yue Feng,Chris M Thompson,Sarah Horwitz,John R Thompson,Euan D MacIntyre,Nancy A Thornberry,Kevin Chapman,Yun-Ping Zhou,Andrew D Howard,Jing Li,

Identification and validation of novel drug targets continues to be a major bottleneck in drug development, particularly for polygenic complex diseases such as type 2 diabetes. Here, the authors describe an approach that allows researchers to rapidly identify and validate potential drug targets by combining chemical tools and RNA interference technology. As a proof-of-concept study, the known mechanism Sigma LOPAC library was used to screen for glucose-dependent insulin secretion (GDIS) in INS-1 832/13 cells. In addition to several mechanisms that are known to regulate GDIS (such as cyclic adenosine monophosphate-specific phosphodiesterases, adrenoceptors, and Ca(2+) channels), the authors find that several of the dopamine receptor (DRD) antagonists significantly enhance GDIS, whereas DRD agonists profoundly inhibit GDIS. Subsequent siRNA studies in the same cell line indicate that knockdown of DRD2 enhanced GDIS. Furthermore, selective DRD2 antagonists and agonists also enhance or suppress, respectively, GDIS in isolated rat islets. The data support that the approach described here offers a rapid and effective way for target identification and validation.

Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing. Publishing Authors By Initials

W Wu,J Shang,Y Feng,CM Thompson,S Horwitz,JR Thompson,ED MacIntyre,NA Thornberry,K Chapman,YP Zhou,AD Howard,J Li,

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Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of biomolecular screening : the official j

VOLUME: 13

Page Numbers: 128-34

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ISSN: 1087-0571

DAY: 23

MONTH: 01

YEAR: 2008

Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing. Information

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LANGUAGE: eng

NlmUniqueID: 9612112

Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing. Keywords Mesh Terms:

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Grant and Affiliation Information for Identification of Glucose-Dependant Insulin Secretion Targets in Pancreatic {beta} Cells by Combining Defined-Mechanism Compound Library Screening and siRNA Gene Silencing.

AFFILIATION: Target Validation.

Country: United States

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MEDLINETA: J Biomol Screen

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