Effects of adrenaline on whole-body glucose metabolism and insulin-mediated regulation of glycogen synthase and PKB phosphorylation in human skeletal muscle.
In the present study, we investigated the effect of adrenaline on insulin-mediated regulation of glucose and fat metabolism with focus on regulation of skeletal muscle PKB, GSK-3, and glycogen synthase (GS) phosphorylation. Ten healthy subjects (5 men and 5 women) received a 240-minute intravenous infusion of adrenaline (0.05 μg/[kg min]) or saline; after 120 minutes, a hyperinsulinemic-euglycemic clamp was added. Adrenaline infusion increased blood glucose concentration by approximately 50%, but the hyperinsulinemic clamp normalized blood glucose within 30 minutes. Glucose infusion rate during the last hour was approximately 60% lower during adrenaline infusion compared with saline (4.3 ± 0.5 vs 11.2 ± 0.6 mg/kg lean body mass per minute). Insulin increased PKB Ser⁴⁷³, PKB Thr³⁰⁸, and GSK-3β Ser⁹ phosphorylation in skeletal muscles; coinfusion of adrenaline did not influence insulin-stimulated PKB and GSK-3 phosphorylation. Adrenaline alone did not influence phosphorylation of PKB and GSK-3β. Insulin increased GS fractional activity and decreased GS Ser⁶⁴¹ and Ser⁶⁴⁵,⁶⁴⁹,⁶⁵³,⁶⁵⁷ phosphorylation. In the presence of adrenaline, insulin did neither activate GS nor dephosphorylate GS Ser⁶⁴¹. Surprisingly, GS Ser⁷ phosphorylation was not influenced by adrenaline. Adrenaline increased plasma lactate concentration; and muscle glycogen content was reduced in skeletal muscle the day after adrenaline infusion, supporting that insulin does not stimulate glycogen synthesis in skeletal muscles when adrenaline is present. In conclusion, adrenaline did not influence basal or insulin-stimulated PKB and GSK-3β phosphorylation in muscles, but completely blocked insulin-mediated GS activation and Ser⁶⁴¹ dephosphorylation. Still, insulin normalized adrenaline-mediated hyperglycemia.
Department of Physiology, National Institute of Occupational Health, P.O. Box 8149 Dep, N-0033 Oslo, Norway. jorgen.jensen@nih.no
Jørgen
J
Jensen
Toralph
T
Ruge
Yu-Chiang
YC
Lai
Maria K
MK
Svensson
Jan W
JW
Eriksson
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000032:analysis; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D019344:Lactic Acid; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose; D004837:Epinephrine