PXD012027-2

PXD012027 is an original dataset announced via ProteomeXchange.

Title	Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists
Description	Pathways modulating glucose homeostasis independently of insulin would open new avenues to combat insulin resistance and diabetes. Here, we report the establishment, characterization and use of a vertebrate 'insulin-free' model to identify insulin-independent modulators of glucose metabolism. insulin knockout zebrafish recapitulate core characteristics of diabetes and survive only up to larval stages. Utilizing a highly efficient endoderm transplant technique, we generated viable chimeric adults that provide the large numbers of insulin mutant larvae required for our screening platform. Using glucose as a disease-relevant readout, we screened 2233 molecules and identified 3 that consistently reduced glucose levels in insulin mutants. Most significantly, we uncovered an insulin-independent beneficial role for androgen receptor antagonism in hyperglycemia, mostly by reducing fasting glucose levels. Our study proposes therapeutic roles for androgen signaling in diabetes and, more broadly, offers a novel in vivo model for rapid screening and decoupling of insulin-dependent and -independent mechanisms.
HostingRepository	PRIDE
AnnounceDate	2018-12-13
AnnouncementXML	Submission_2018-12-13_04:06:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anna Sokol
SpeciesList	scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-12 01:24:37	ID requested
1	2018-12-13 01:33:42	announced
⏵ 2	2018-12-13 04:07:01	announced	Updated project metadata.

Mullapudi ST, Helker CS, Boezio GL, Maischein HM, Sokol AM, Guenther S, Matsuda H, Kubicek S, Graumann J, Yang YHC, Stainier DY, Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists. Elife, 7():(2018) [pubmed]

curator keyword: Biological

submitter keyword: metabolism, glucose homeostasis, insuline mutant, chemical screen, zebrafish

Didier Y. R. Stainier
contact affiliation	Department of Developmental Genetics Max Planck Institute for Heart and Lung Research Ludwigstrasse 43 61231 Bad Nauheim Germany
contact email	Didier.Stainier@mpi-bn.mpg.de
lab head
Anna Sokol
contact affiliation	Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
contact email	anna.sokol@mpi-bn.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD012027

PRIDE project URI

• PRIDE
  1. PXD012027
     1. Label: PRIDE project
     2. Name: Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists