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Carper, D.* ; Lac, M.* ; Coue, M.* ; Labour, A.* ; Märtens, A.* ; Banda, J.A.A.* ; Mazeyrie, L.* ; Mechta, M.* ; Ingerslev, L.R.* ; Elhadad, M.A. ; Petit, J.V.* ; Maslo, C.* ; Monbrun, L.* ; Del Carmine, P.* ; Sainte-Marie, Y.* ; Bourlier, V.* ; Laurens, C.* ; Mithieux, G.* ; Joanisse, D.R.* ; Coudray, C.* ; Feillet-Coudray, C.* ; Montastier, E.* ; Viguerie, N.* ; Tavernier, G.* ; Waldenberger, M. ; Peters, A. ; Wang-Sattler, R. ; Adamski, J. ; Suhre, K.* ; Gieger, C. ; Kastenmüller, G. ; Illig, T.* ; Lichtinghagen, R.* ; Seissler, J.* ; Mounier, R.* ; Hiller, K.* ; Jordan, J.* ; Barrès, R.* ; Kuhn, M.* ; Pesta, D.* ; Moro, C.*

Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity.

Sci. Adv. 10:eadl4374 (2024)

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Type 2 diabetes (T2D) and obesity are strongly associated with low natriuretic peptide (NP) plasma levels and a down-regulation of NP guanylyl cyclase receptor-A (GCA) in skeletal muscle and adipose tissue. However, no study has so far provided evidence for a causal link between atrial NP (ANP)/GCA deficiency and T2D pathogenesis. Here, we show that both systemic and skeletal muscle ANP/GCA deficiencies in mice promote metabolic disturbances and prediabetes. Skeletal muscle insulin resistance is further associated with altered mitochondrial function and impaired endurance running capacity. ANP/GCA-deficient mice exhibit increased proton leak and reduced content of mitochondrial oxidative phosphorylation proteins. We further show that GCA is related to several metabolic traits in T2D and positively correlates with markers of oxidative capacity in human skeletal muscle. Together, these results indicate that ANP/GCA signaling controls muscle mitochondrial integrity and oxidative capacity in vivo and plays a causal role in the development of prediabetes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Skeletal-muscle; Oxidative Stress; Obesity; Sensitivity; Population; Expression; Platform; Program; Enhance; Kora

ISSN (print) / ISBN 2375-2548

e-ISSN 2375-2548

Journal Science Advances

Quellenangaben Volume: 10, Issue: 41, Article Number: eadl4374

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place Washington, DC [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
Institute of Experimental Genetics (IEG)
Institute of Computational Biology (ICB)

Grants Inserm/Occitanie Region
Fondation pour la Recherche Medicale
Agence nationale de la Recherche
EFSd/Boehringer ingelheim european Research Programme on "Multi- System Challenges in diabetes"
Educational grant from MSd
European Foundation
Societe Francophone du diabete
Inserm