Nature Communications (Jul 2022)
Hepatic non-parenchymal S100A9-TLR4-mTORC1 axis normalizes diabetic ketogenesis
- Gloria Ursino,
- Giorgio Ramadori,
- Anna Höfler,
- Soline Odouard,
- Pryscila D. S. Teixeira,
- Florian Visentin,
- Christelle Veyrat-Durebex,
- Giulia Lucibello,
- Raquel Firnkes,
- Serena Ricci,
- Claudia R. Vianna,
- Lin Jia,
- Mirjam Dirlewanger,
- Philippe Klee,
- Joel K. Elmquist,
- Johannes Roth,
- Thomas Vogl,
- Valérie M. Schwitzgebel,
- François R. Jornayvaz,
- Andreas Boland,
- Roberto Coppari
Affiliations
- Gloria Ursino
- Department of Cell Physiology and Metabolism, University of Geneva
- Giorgio Ramadori
- Department of Cell Physiology and Metabolism, University of Geneva
- Anna Höfler
- Department of Molecular Biology, University of Geneva
- Soline Odouard
- Department of Cell Physiology and Metabolism, University of Geneva
- Pryscila D. S. Teixeira
- Department of Cell Physiology and Metabolism, University of Geneva
- Florian Visentin
- Department of Cell Physiology and Metabolism, University of Geneva
- Christelle Veyrat-Durebex
- Department of Cell Physiology and Metabolism, University of Geneva
- Giulia Lucibello
- Department of Cell Physiology and Metabolism, University of Geneva
- Raquel Firnkes
- Department of Cell Physiology and Metabolism, University of Geneva
- Serena Ricci
- Department of Cell Physiology and Metabolism, University of Geneva
- Claudia R. Vianna
- Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas
- Lin Jia
- Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas
- Mirjam Dirlewanger
- Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, Obstetrics and Gynecology, University Hospitals of Geneva
- Philippe Klee
- Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, Obstetrics and Gynecology, University Hospitals of Geneva
- Joel K. Elmquist
- Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas
- Johannes Roth
- Institute of Immunology, University of Munster
- Thomas Vogl
- Institute of Immunology, University of Munster
- Valérie M. Schwitzgebel
- Department of Cell Physiology and Metabolism, University of Geneva
- François R. Jornayvaz
- Diabetes Center of the Faculty of Medicine, University of Geneva
- Andreas Boland
- Department of Molecular Biology, University of Geneva
- Roberto Coppari
- Department of Cell Physiology and Metabolism, University of Geneva
- DOI
- https://doi.org/10.1038/s41467-022-31803-5
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
Excess ketogenesis can lead to ketoacidosis, a serious complication in patients with diabetes. Here the authors report an insulin independent pathway, the hepatic nonparenchymal S100A9-TLR4-mTORC1 axis, that is able to normalize diabetic ketogenesis and pre-clinical data to suggest potential for development of S100A9 based adjunctive therapy to insulin.