20.500.12556/RUL-182453 Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity 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. atrial natriuretic peptide insulin resistance mitochondrial dysfunction low endurance capacity atrijski natriuretični peptid inzulinska rezistenca mitohondrijska disfunkcija nizka vzdržljivostna zmogljivost true false true Angleški jezik Slovenski jezik Članek v reviji 2026-05-12 11:22:17 2026-05-12 11:22:24 2026-10-05 09:12:32 0000-00-00 00:00:00 2024 0 0 18 str. iss. 41, art. eadl4374 Vol. 10 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577:61 2375-2548 10.1126/sciadv.adl4374 265224195 sciadv.adl4374.pdf sciadv.adl4374.pdf 1 810062C69F6EF669B467C4B7DF761932 d991c3c3588050fc1ef2c8fbe19bee0db9e8517c4ac66e2290ca9464aec1ff9e 1c1e8a49-5e4d-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234815 https://www.science.org/doi/10.1126/sciadv.adl4374 0 eef91c2e-5a89-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=234613 Medicinska fakulteta 0 0 0