PXD047140

PXD047140 is an original dataset announced via ProteomeXchange.

Title	Sustained hyperglycemia specifically targets translation of mRNAs for insulin secretion
Description	Pancreatic beta-cells are specialized for coupling glucose metabolism to insulin peptide production and secretion. Acute glucose exposure robustly and coordinately increases translation of proinsulin and proteins required for secretion of mature insulin peptide. By contrast, chronically elevated glucose levels that occur during diabetes impair beta-cell insulin secretion and have been shown experimentally to suppress insulin translation. Whether translation of other genes critical for insulin secretion are similarly downregulated by chronic high glucose is unknown. Here, we used high-throughput ribosome profiling and nascent proteomics in MIN6 insulinoma cells to elucidate the genome-wide impact of sustained high glucose on -cell mRNA translation. Prior to induction of ER stress or suppression of global translation, sustained high glucose suppressed glucose-stimulated insulin secretion and downregulated translation of not only insulin, but also of mRNAs related to insulin secretory granule formation, exocytosis, and metabolism-coupled insulin secretion. Translation of these mRNAs was also downregulated in primary rat and human islets following ex-vivo incubation with sustained high glucose and in an in vivo model of chronic mild hyperglycemia. Furthermore, translational downregulation decreased cellular abundance of these proteins. Our study uncovered a translational regulatory circuit during beta-cell glucose toxicity that impairs expression of proteins with critical roles in beta-cell function.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:16:42.738.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Abigael Cheruiyot
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-21 14:14:57	ID requested
1	2023-12-03 14:06:51	announced
⏵ 2	2024-10-22 06:16:43	announced	2024-10-22: Updated project metadata.

Cheruiyot A, Hollister-Lock J, Sullivan B, Pan H, Dreyfuss JM, Bonner-Weir S, Schaffer JE, Sustained hyperglycemia specifically targets translation of mRNAs for insulin secretion. J Clin Invest, 134(3):(2023) [pubmed]

10.1172/jci173280;

submitter keyword: nascent proteomics,glucose toxicity, ribosome profiling, islets, mRNA translation, pancreatic -cells

Jean E. Schaffer
contact affiliation	Joslin Diabetes Center/Harvard Medical School
contact email	schafferj@joslin.harvard.edu
lab head
Abigael Cheruiyot
contact affiliation	Joslin Diabetes Center/Harvard Medical School
contact email	abigael.cheruiyot@joslin.harvard.edu
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/2023/12/PXD047140

PRIDE project URI

• PRIDE
  1. PXD047140
     1. Label: PRIDE project
     2. Name: Sustained hyperglycemia specifically targets translation of mRNAs for insulin secretion