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000168147 1001_ $$aOkun, Jürgen G$$b0
000168147 245__ $$aLiver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.
000168147 260__ $$a[London]$$bSpringer Nature$$c2021
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000168147 520__ $$aBoth obesity and sarcopenia are frequently associated in ageing, and together may promote the progression of related conditions such as diabetes and frailty. However, little is known about the pathophysiological mechanisms underpinning this association. Here we show that systemic alanine metabolism is linked to glycaemic control. We find that expression of alanine aminotransferases is increased in the liver in mice with obesity and diabetes, as well as in humans with type 2 diabetes. Hepatocyte-selective silencing of both alanine aminotransferase enzymes in mice with obesity and diabetes retards hyperglycaemia and reverses skeletal muscle atrophy through restoration of skeletal muscle protein synthesis. Mechanistically, liver alanine catabolism driven by chronic glucocorticoid and glucagon signalling promotes hyperglycaemia and skeletal muscle wasting. We further provide evidence for amino acid-induced metabolic cross-talk between the liver and skeletal muscle in ex vivo experiments. Taken together, we reveal a metabolic inter-tissue cross-talk that links skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.
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000168147 7001_ $$aRusu, Patricia M$$b1
000168147 7001_ $$aChan, Andrea Y$$b2
000168147 7001_ $$00000-0002-1762-1896$$aWu, Yuqin$$b3
000168147 7001_ $$aYap, Yann W$$b4
000168147 7001_ $$aSharkie, Thomas$$b5
000168147 7001_ $$0P:(DE-HGF)0$$aSchumacher, Jonas$$b6
000168147 7001_ $$aSchmidt, Kathrin V$$b7
000168147 7001_ $$aRoberts-Thomson, Katherine M$$b8
000168147 7001_ $$aRussell, Ryan D$$b9
000168147 7001_ $$aZota, Annika$$b10
000168147 7001_ $$aHille, Susanne$$b11
000168147 7001_ $$aJungmann, Andreas$$b12
000168147 7001_ $$0P:(DE-He78)b9f6e98404bac02f2318460886771357$$aMaggi, Ludovico$$b13
000168147 7001_ $$aLee, Young$$b14
000168147 7001_ $$00000-0003-0208-2065$$aBlüher, Matthias$$b15
000168147 7001_ $$0P:(DE-He78)e527f794b23172e769c8904180546f57$$aHerzig, Stephan$$b16
000168147 7001_ $$aKeske, Michelle A$$b17
000168147 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwälder, Mathias$$b18$$udkfz
000168147 7001_ $$aMüller, Oliver J$$b19
000168147 7001_ $$0P:(DE-He78)fcdc7b4207660a1372d0cd5491ad856e$$aRose, Adam John$$b20$$eLast author
000168147 773__ $$0PERI:(DE-600)2933873-6$$a10.1038/s42255-021-00369-9$$gVol. 3, no. 3, p. 394 - 409$$n3$$p394 - 409$$tNature metabolism$$v3$$x2522-5812$$y2021
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