PXD053975

PXD053975 is an original dataset announced via ProteomeXchange.

Title	Fructose-bisphosphatase 1 (FBP1) is a target of the antihyperglycemic action of salicylate
Description	Widespread use of the ancient drug salicylate for diabetes in humans has been prevented by challenging side effects of the drug, and continuing uncertainty about the relevant enzyme target(s), against which other drugs could then be developed. Here, we identify fructose-1,6-bisphosphatase 1 (FBP1) as an important contributor to the anti-hyperglycaemic action of salicylate. Compared with wild-type littermates, AMP-insensitive FBP1 knockin (KI) mice, were resistant to effects of the drug on body weight, fasting glucose, glucose tolerance, pyruvate disposal and glucose production. Relative disinhibition of gluconeogenesis in KI hepatocytes led to reductions in TCA cycle activity, linking insulin resistance and its reversal, to non-carbohydrate fuel management. Taken together with previous findings on metformin, the accidental discovery on at least two independent occasions of diabetes drugs capable of promoting allosteric FBP1 inhibition, highlight this target as a highly promising target for prospective rational drug discovery approaches.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-25_16:29:54.551.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Raid Nisr
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-16 03:06:01	ID requested
⏵ 1	2025-05-25 16:29:55	announced

Nisr RB, Atrih A, Lara EJG, Lamont D, Luda KM, McCrimmon RJ, Sakamoto K, Rena G, McNeilly AD, The Ancient Drug Salicylate Indirectly Targets Fructose-1,6-Bisphosphatase to Suppress Liver Glucose Production in Diet-Induced Obese Mice. Acta Physiol (Oxf), 241(6):e70058(2025) [pubmed]

10.1111/apha.70058;

ProteomeXchange project tag: Diabetes (B/D-HPP), Human Proteome Project

submitter keyword: Salicylate, AMP,FBP1

Graham Rena
contact affiliation	School Of Medicin University of Dundee
contact email	g.rena@dundee.ac.uk
lab head
Raid Nisr
contact affiliation	postdoctoral researcher
contact email	r.b.nisr@dundee.ac.uk
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/2025/05/PXD053975

PRIDE project URI

• PRIDE
  1. PXD053975
     1. Label: PRIDE project
     2. Name: Fructose-bisphosphatase 1 (FBP1) is a target of the antihyperglycemic action of salicylate