Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Artemisinins Target GABAA Receptor Signaling and Impair α Cell Identity.

Cell | Jan 12, 2017

Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm. We show that the protein gephyrin is the mammalian target of these antimalarial drugs and that the mechanism of action of these molecules depends on the enhancement of GABAA receptor signaling. Our results in zebrafish, rodents, and primary human pancreatic islets identify gephyrin as a druggable target for the regeneration of pancreatic β cell mass from α cells.

Pubmed ID: 27916275 RIS Download

Mesh terms: Animals | Artemisinins | Carrier Proteins | Cell Transdifferentiation | Cells, Cultured | Diabetes Mellitus | Diabetes Mellitus, Type 1 | Disease Models, Animal | Gene Expression Profiling | Homeodomain Proteins | Humans | Insulin | Islets of Langerhans | Membrane Proteins | Mice | Protein Stability | Rats | Receptors, GABA-A | Signal Transduction | Single-Cell Analysis | Transcription Factors | Zebrafish | gamma-Aminobutyric Acid

Research resources used in this publication

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: UC4 DK098085

Antibody Registry (Reagent, Antibodies)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


GE Healthcare

A commercial antibody supplier and provider of various services.

tool

View all literature mentions

ATCC

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

tool

View all literature mentions

Bio-Rad Laboratories

A commercial instrument and chemical vendor.

tool

View all literature mentions

QIAGEN

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

tool

View all literature mentions

TopHat

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using the ultra high-throughput short read aligner Bowtie, and then analyzes the mapping results to identify splice junctions between exons.

tool

View all literature mentions

Fiji

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

tool

View all literature mentions

Gene Set Enrichment Analysis

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

tool

View all literature mentions

ImageJ

Software tool as an open source Java-based image processing program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

tool

View all literature mentions

RSeQC

Software package to comprehensively evaluate different aspects of RNA-seq experiments, such as sequence quality, GC bias, polymerase chain reaction bias, nucleotide composition bias, sequencing depth, strand specificity, coverage uniformity and read distribution over the genome structure. RSeQC takes both SAM and BAM files as input, which can be produced by most RNA-seq mapping tools as well as BED files, which are widely used for gene models.

tool

View all literature mentions

SigmaPlot

Statistical analysis and scientific graphing software for Windows OS.

tool

View all literature mentions

RefSeq

Database that provides a comprehensive, integrated, non-redundant, well-annotated set of sequences, including genomic DNA, transcripts, and proteins. It provides a stable reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis (especially RefSeqGene records), expression studies, and comparative analyses. Included are sequences from plasmids, organelles, viruses, archaea, bacteria, and eukaryotes. Each RefSeq is constructed wholly from sequence data submitted to the International Nucleotide Sequence Database Collaboration (INSDC). It is a unique resource because it provides a large, multi-species, curated sequence database representing separate but explicitly linked records from genomes to transcripts and translation products, as appropriate. Unlike the sequence redundancy found in the public sequence repositories that comprise the INSDC, (i.e., NCBI's GenBank, the European Nucleotide Archive, and the DNA Data Bank of Japan), the RefSeq collection aims to provide, for each included species, a complete set of non-redundant, extensively cross-linked, and richly annotated nucleic acid and protein records. It is recognized, however, that the coverage and finishing of public sequence data varies from organism to organism so intermediate genomic records are provided in some circumstances. The RefSeq collection is available without restriction and can be retrieved in several different ways, such as by searching or by available links in NCBI resources, including PubMed, Nucleotide, Protein, Gene, and Map Viewer, searching with a sequence via BLAST, and downloading from the RefSeq FTP site.

tool

View all literature mentions

Adobe Illustrator

Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.

tool

View all literature mentions

ProteoWizard

Software that enables rapid tool creation by providing a robust, pluggable development framework that simplifies and unifies data file access, and performs standard proteomics and LCMS dataset computations.

tool

View all literature mentions

Thermo Xcalibur

A software which acquires and processes data sets, primarily through the Xcalibur system.

tool

View all literature mentions