PXD052854-1

PXD052854 is an original dataset announced via ProteomeXchange.

Title	Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system
Description	Current research on metabolic disorders and diabetes relies on animal models because multi-organ diseases cannot be well studied with the standard in vitro assays. Here, we connect models of key metabolic organs, pancreas and liver, on a microfluidic chip to enable diabetes research in a human-based in vitro system. Aided by mechanistic mathematical modelling, we show that hyperglycemia and high cortisone induce glucose dysregulation in the pancreas-liver microphysiological system (MPS) mimicking a diabetic phenotype seen in patients with glucocorticoid-induced diabetes. In this diseased condition, pancreas-liver MPS displays beta-cell dysfunction, steatosis, elevated ketone-body secretion, increased glycogen storage, and upregulated gluconeogenic gene expression. In turn, a physiological culture condition maintains the glucose tolerance and beta cell function. This method was evaluated for reproducibility in two laboratories and was effective in multiple pancreatic islet donors. The model also provides a platform to identify new therapeutic proteins as demonstrated with a combined transcriptome and proteome analysis.
HostingRepository	PRIDE
AnnounceDate	2024-08-11
AnnouncementXML	Submission_2024-08-10_16:14:23.057.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Fuchs
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-05 04:25:42	ID requested
⏵ 1	2024-08-10 16:14:23	announced

10.1038/s42003-024-06514-w;

submitter keyword: Type 2 diabetes mellitus, Metabolic disorders, Microphysiological system, Human pancreatic islets, Glucocorticoids, Hyperglycemia, Transcriptomics,Diabetes, Proteomics, Liver, Pancreas

Sara F. Hansson
contact affiliation	AstraZeneca
contact email	sara.hansson@astrazeneca.com
lab head
Johannes Fuchs
contact affiliation	Gothenburg University
contact email	johannes.fuchs@gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052854
     1. Label: PRIDE project
     2. Name: Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system