The genetic and dietary landscape of the muscle insulin signalling network.

Autor:	van Gerwen J; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Masson SWC; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Cutler HB; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Vegas AD; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Potter M; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Stöckli J; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Madsen S; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Nelson ME; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., Humphrey SJ; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia., James DE; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.; Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Feb 08; Vol. 12. Date of Electronic Publication: 2024 Feb 08.
DOI:	10.7554/eLife.89212
Abstrakt:	Metabolic disease is caused by a combination of genetic and environmental factors, yet few studies have examined how these factors influence signal transduction, a key mediator of metabolism. Using mass spectrometry-based phosphoproteomics, we quantified 23,126 phosphosites in skeletal muscle of five genetically distinct mouse strains in two dietary environments, with and without acute in vivo insulin stimulation. Almost half of the insulin-regulated phosphoproteome was modified by genetic background on an ordinary diet, and high-fat high-sugar feeding affected insulin signalling in a strain-dependent manner. Our data revealed coregulated subnetworks within the insulin signalling pathway, expanding our understanding of the pathway's organisation. Furthermore, associating diverse signalling responses with insulin-stimulated glucose uptake uncovered regulators of muscle insulin responsiveness, including the regulatory phosphosite S469 on Pfkfb2, a key activator of glycolysis. Finally, we confirmed the role of glycolysis in modulating insulin action in insulin resistance. Our results underscore the significance of genetics in shaping global signalling responses and their adaptability to environmental changes, emphasising the utility of studying biological diversity with phosphoproteomics to discover key regulatory mechanisms of complex traits. Competing Interests: Jv, SM, HC, AV, MP, JS, SM, MN, SH, DJ No competing interests declared (© 2023, van Gerwen et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu