Steen Bønløkke Pedersen

Insulin inhibits autophagy signaling independent of counter-regulatory hormone levels, but does not affect the effects of exercise

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Acute exercise increases autophagic signaling through ULK1 in human skeletal muscle during both anabolic and catabolic conditions. The aim of the present study was to investigate if changes in ULK1 Ser555 phosphorylation during exercise are reflected by changes in phosphorylation of a newly identified ULK1 substrate (ATG14 Ser29), and to elucidate the involvement of circulatory hormones in regulation of autophagy in human skeletal muscle. We show that one hour of cycling exercise increases ATG14 Ser29 phosphorylation during both hyperinsulinemic euglycemic and euinsulinemic euglycemic conditions. This could suggest that counter-regulatory hormones stimulate autophagy in skeletal muscle, as circulating concentrations of these hormones are highly elevated during exercise. Furthermore, ATG14 Ser29 correlated positively with ULK1 phosphorylation, suggesting that ULK1 Ser555 (activating site) phosphorylation reflects ULK1 kinase activity. In a separate series of experiments, we show that insulin stimulates ULK1 phosphorylation at Ser757 (inhibitory site) in both hypoglycemic and euglycemic conditions, suggesting that counter-regulatory hormones (such as epinephrine, norepinephrine, growth hormone and glucagon) have limited effects on autophagy signaling in human skeletal muscle. In conclusion, one hour of cycling exercise increases phosphorylation of ATG14 at Ser29 in a pattern that mirrors ULK1 phosphorylation at Ser555. Moreover, insulin effects on autophagy signaling in human skeletal muscle are independent of hypoglycemic and euglycemic conditions.

TidsskriftJournal of applied physiology (Bethesda, Md. : 1985)
Sider (fra-til)1204-1209
Antal sider6
StatusUdgivet - 2018

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