TY - JOUR

T1 - Epinephrine-stimulated glycogen breakdown activates glycogen synthase and increases insulin-stimulated glucose uptake in epitrochlearis muscles

AU - Kolnes, Anders J

AU - Birk, Jesper Bratz

AU - Eilertsen, Einar

AU - Stuenæs, Jorid T

AU - Wojtaszewski, Jørgen

AU - Jensen, Jørgen

N1 - CURIS 2015 NEXS 049

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1152/ajpendo.00282.2014

DO - 10.1152/ajpendo.00282.2014

M3 - Journal article

C2 - 25465888

VL - 308

SP - E231-E240

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 3

ER -