A multiorgan map of metabolic, signaling, and inflammatory pathways that coordinately control fasting glycemia in mice
To identify the pathways that are coordinately regulated in pancreatic β cells, muscle, liver, and fat to control fasting glycemia we fed C57Bl/6, DBA/2, and Balb/c mice a regular chow or a high fat diet for 5, 13, and 33 days. Physiological, transcriptomic and lipidomic data were used in a data fusion approach to identify organ-specific pathways linked to fasting glycemia across all conditions investigated. In pancreatic islets, constant insulinemia despite higher glycemic levels was associated with reduced expression of hormone and neurotransmitter receptors, OXPHOS, cadherins, integrins, and gap junction mRNAs. Higher glycemia and insulin resistance were associated, in muscle, with decreased insulin signaling, glycolytic, Krebs' cycle, OXPHOS, and endo/exocytosis mRNAs; in hepatocytes, with reduced insulin signaling, branched chain amino acid catabolism and OXPHOS mRNAs; in adipose tissue, with increased innate immunity and lipid catabolism mRNAs. These data provide a resource for further studies of interorgan communication in glucose homeostasis.
Authors
- Kai Simons (ORCID: https://orcid.org/0000-0002-9231-9996)
- Mark Ibberson (ORCID: https://orcid.org/0000-0003-3152-5670)
- Marco Pagni (ORCID: https://orcid.org/0000-0001-9292-9463)
- Ana Rodríguez Sánchez-Archidona (ORCID: https://orcid.org/0000-0001-6002-2779)
- Céline Cruciani‐Guglielmacci (ORCID: https://orcid.org/0000-0002-2562-5360)
- Florence Mehl (ORCID: https://orcid.org/0000-0002-9619-1707)
- Jessica Denom (ORCID: https://orcid.org/0000-0002-8507-058X)
- Leonore Wigger (ORCID: https://orcid.org/0000-0001-5230-0265)
- Hervé Le Stunff (ORCID: https://orcid.org/0000-0003-4618-7838)
- Justine Lallement
- Christian Klose (ORCID: https://orcid.org/0000-0003-2853-4533)
- Mathias J. Gerl (ORCID: https://orcid.org/0000-0002-8074-7221)
- Kelly Meneyrol
- Bernard Thorens (ORCID: https://orcid.org/0000-0002-3738-0129)
- Chr̀istophe Magnan (ORCID: https://orcid.org/0000-0002-7044-2571)
- Ida Meitil
Institutions
- SIB Swiss Institute of Bioinformatics (CH)
- Centre National de la Recherche Scientifique (FR)
- Université Paris Cité (FR)
- Unit of Functional and Adaptive Biology (FR)
- University of Lausanne (CH)
Publication Details
- Journal
- iScience
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1016/j.isci.2024.111134
- Citations
- 2
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 1.15
Funders
- National Science Foundation
- European Federation of Pharmaceutical Industries and Associations
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Innovative Medicines Initiative
- Horizon 2020 Framework Programme
- Staatssekretariat für Bildung, Forschung und Innovation