Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
18 Jul 2024
18 Jul 2024
Historique:
received:
18
06
2023
accepted:
26
06
2024
medline:
19
7
2024
pubmed:
19
7
2024
entrez:
18
7
2024
Statut:
epublish
Résumé
Current research on metabolic disorders and diabetes relies on animal models because multi-organ diseases cannot be well studied with standard in vitro assays. Here, we have connected cell models of key metabolic organs, the pancreas and liver, on a microfluidic chip to enable diabetes research in a human-based in vitro system. Aided by mechanistic mathematical modeling, we demonstrate that hyperglycemia and high cortisone concentration 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, the pancreas-liver MPS displays beta-cell dysfunction, steatosis, elevated ketone-body secretion, increased glycogen storage, and upregulated gluconeogenic gene expression. Conversely, a physiological culture condition maintains glucose tolerance and beta-cell function. This method was reproducible 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.
Identifiants
pubmed: 39025915
doi: 10.1038/s42003-024-06514-w
pii: 10.1038/s42003-024-06514-w
doi:
Substances chimiques
Cortisone
V27W9254FZ
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
877Subventions
Organisme : Stiftelsen för Strategisk Forskning (Swedish Foundation for Strategic Research)
ID : ITM17-0245
Organisme : Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)
ID : 2020.0182
Organisme : Stiftelsen Forska Utan Djurförsök (Swedish Fund for Research Without Animal Experiments)
ID : F2019-0010
Organisme : VINNOVA (Swedish Governmental Agency for Innovation Systems)
ID : 2020-04711
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2018-05418, 2018-03319
Informations de copyright
© 2024. The Author(s).
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