Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

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Adrenaline increases glycogen synthase (GS) phosphorylation and decreases GS activity but also stimulates glycogen breakdown and low glycogen content normally activates GS. To test the hypothesis that glycogen content directly regulates GS phosphorylation, glycogen breakdown was stimulated in condition with decreased GS activation. Saline or adrenaline (0.02mg/100g rat) was injected subcutaneously in Wistar rats (~130 g) with low (24 h fasted), normal (normal diet) and high glycogen content (fasted-refed) and epitrochlearis muscles were removed after 3 h and incubated ex vivo eliminating adrenaline action. Adrenaline injection reduced glycogen content in epitrochlearis muscles with high (120.7±17.8 vs 204.6±14.5 mmol•kg(-1); p<0.01) and normal glycogen (89.5±7.6 vs 152.6±8.1 mmol•kg(-1); p<0.01), but not significantly in muscles with low glycogen (90.0±5.0 vs 102.8±7.8 mmol•kg(-1); p=0.17). In saline-injected rats, GS phosphorylation at sites 2+2a, 3a+3b and 1b was higher and GS activity lower in muscles with high compared to low glycogen. GS site 2+2a and 3a+3b phosphorylation decreased and GS activity increased in muscles where adrenaline decreased glycogen content; these parameters were unchanged in epitrochlearis from fasted rats where adrenaline injection did not decrease glycogen content. Incubation with insulin decreased GS site 3a+3b phosphorylation independent of glycogen content. Insulin-stimulated glucose uptake was increased in muscles where adrenaline injection decreased glycogen content. In conclusion, adrenaline stimulates glycogenolysis in epitrochlearis muscles with normal and high, but not low glycogen content. Adrenaline-stimulated glycogenolysis decreased GS phosphorylation and increased GS activity. These data for the first time document direct regulation of GS phosphorylation by glycogen content.

TidsskriftAmerican Journal of Physiology: Endocrinology and Metabolism
Udgave nummer3
Sider (fra-til)E231-E240
Antal sider10
StatusUdgivet - 2015

Bibliografisk note

CURIS 2015 NEXS 049

ID: 130291663