Evidence mapPaperPMID 39025915Full record

ArticleCommunications biology2024

Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system.

Sophie Rigal, Belén Casas, Kajsa P Kanebratt, Charlotte Wennberg Huldt, Lisa U Magnusson, Erik Müllers, Fredrik Karlsson, Maryam Clausen, Sara F Hansson, Louise Leonard and 8 more

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Sophie RigalTissUse GmbH, Berlin, Germany.
Belén CasasDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Kajsa P KanebrattDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Charlotte Wennberg HuldtBioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Lisa U MagnussonBioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Erik MüllersBioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0002-2176-3248
Fredrik KarlssonData Sciences and Quantitative Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
Maryam ClausenTranslational Genomics, Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
Sara F HanssonTranslational Science and Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Louise LeonardData Sciences and Quantitative Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
Jonathan CairnsData Sciences and Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-9982-1401
Rasmus Jansson LöfmarkDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Carina ÄmmäläBioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Uwe MarxTissUse GmbH, Berlin, Germany.
Peter GennemarkDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0002-7865-7454
Gunnar CedersundDepartment of Biomedical Engineering, Linköping University, Linköping, Sweden.
Tommy B AnderssonDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Liisa K VilénDrug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. liisa.vilen@astrazeneca.com.ORCID 0000-0001-9184-4847

Funding

Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation) 2020.0182Stiftelsen Forska Utan Djurförsök (Swedish Fund for Research Without Animal Experiments) F2019-0010Stiftelsen för Strategisk Forskning (Swedish Foundation for Strategic Research) ITM17-0245Vetenskapsrådet (Swedish Research Council) 2018-05418, 2018-03319VINNOVA (Swedish Governmental Agency for Innovation Systems) 2020-04711
6 · The paper itself

Abstract

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.

Indexed as

CortisoneGlucoseHomeostasisLiverPancreasHumansInsulin-Secreting CellsLab-On-A-Chip DevicesMicrophysiological SystemsCortisoneGlucose

Identifiers

PMID39025915
PMCPMC11258270

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.