| Title: |
Beta-cell adaptation unveiled: The role of myokines in insulin-resistant mice |
| Authors: |
Liboz, Alexandrine; Beaupère, Carine; Roblot, Natacha; Rousseau, Emma; Tinevez, Jean-Yves; Guilmeau, Sandra; Burnol, Anne-Françoise; Gueddouri, Dalale; Prieur, Xavier; Annicotte, Jean-Sébastien; Macdonald, Tara, L; Fève, Bruno; Guillemain, Ghislaine; Blondeau, Bertrand |
| Contributors: |
Centre de Recherche Saint-Antoine (CRSA); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition CHU Pitié Salpêtrière (IHU ICAN); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Hub d'analyse d'images - Image Analysis Hub (Platform) (IAH); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut du Thorax CHU Nantes (CHU Thorax); Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); University of Toronto; Centre de Référence Maladies Rares - Pathologies de la Résistance à l’Insuline et de l’Insulino-Sensibilité (CRMR PRISIS); CHU Saint-Antoine AP-HP; This work was funded by Inserm, Sorbonne Université, Fondation pour la Recherche Médicale (FRM EQU201903007868 and FRM EQU202103012732), Société Francophone du Diabète, Aide aux Jeunes Diabétiques, Type 1 Running Team, and World Diabetes Tour. We gratefully acknowledge the UtechS Photonic BioImaging (Imagopole), especially Julien Fernandes, C2RT, and Institut Pasteur. We acknowledge the France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INBS-04). The authors thank T. Ledent, L. Dinard, A. Guyomard, T. Coulais, and Q. Pointout (animal housing facility, Saint-Antoine Research Center, Sorbonne University, INSERM, Paris); R. Morrichon (Cell Imaging and Confocal Microscopy Platform); and Elodie Carotine. A.L. was supported by a doctoral fellowship from Ministère de l’Enseignement Supérieur et de la Recherche and Société Francophone du Diabète. |
| Source: |
ISSN: 2211-1247. |
| Publisher Information: |
CCSD; Elsevier Inc |
| Publication Year: |
2025 |
| Subject Terms: |
CP: Metabolism; beta-cell mass adaptation; glucocorticoids; insulin resistance; interorgan crosstalk; kinome analysis; light-sheet 3D microscopy; mouse model; myokines; pancreatic adaptation; [SDV]Life Sciences [q-bio]; [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism |
| Description: |
International audience ; Pancreatic beta cells can adapt their mass and function to maintain normal glycemia when facing peripheral insulin resistance. To clarify the specific contribution and mechanisms of beta-cell mass adaptation in response to insulin resistance, we took advantage of genetic and pharmacologically induced insulin resistance in mice. We uncovered beta-cell expansion, via an increase in pancreatic islet density, as an adaptive mechanism triggered by mild-to-severe insulin resistance in young and older mice and documented pancreatic adaptation using 3D whole-pancreas analysis. Next, we found that insulin-resistant myotubes secrete factors that induce beta-cell differentiation. Using a combination of transcriptomic and functional analysis on a pancreatic differentiation model, we identified that myostatin, amphiregulin, and epiregulin can induce beta-cell differentiation in vitro. This work highlights how a physiological adaptation to insulin resistance can unlock the regenerative potential of myotube-derived peptides to trigger adaptive pancreatic beta-cell mass increase. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.17632/3c954wd6k6.1; info:eu-repo/semantics/altIdentifier/pmid/40946310; PUBMED: 40946310 |
| DOI: |
10.1016/j.celrep.2025.116283 |
| Availability: |
https://pasteur.hal.science/pasteur-05264583; https://pasteur.hal.science/pasteur-05264583v1/document; https://pasteur.hal.science/pasteur-05264583v1/file/1-s2.0-S221112472501054X-main.pdf; https://doi.org/10.1016/j.celrep.2025.116283 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.346CFA63 |
| Database: |
BASE |