Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle.
The effect of epinephrine (E) infusion on insulin-mediated glucose metabolism in humans has been studied. Eight glucose-tolerant men were studied on two separate occasions: 1) during 120 min of euglycemic hyperinsulinemia (UH, approximately 5 mM; 40 mU.m-2.min-1); and 2) during UH while E was infused (UHE, 0.05 microgram.kg-1.min-1). Biopsies were taken from the quadriceps femoris muscle before and after each clamp. Glucose disposal, correcting for endogenous glucose production, was 36 +/- 3 and 18 +/- 2 (SE) mumol.kg fat-free mass (FFM)-1.min-1 during the last 40 min of UH and UHE, respectively (P less than 0.001). Nonoxidative glucose disposal (presumably glycogenesis) averaged 23.0 +/- 3.0 and 4.0 +/- 1.1 (P less than 0.001), whereas carbohydrate oxidation (which is proportional to glycolysis) averaged 13.1 +/- 1.4 and 15.3 +/- 1.1 mumol.kg FFM-1.min-1 (P less than 0.05) during UH and UHE, respectively. UHE resulted in significantly higher contents of UDP-glucose, hexose monophosphates, postphosphofructokinase intermediates, and glucose 1,6-bisphosphate (G-1,6-P2) in muscle (P less than 0.05-0.001), but there were no significant differences in high-energy phosphates or fructose 2,6-bisphosphate (F-2,6-P2) between treatments. Fractional activities of phosphorylase increased (P less than 0.01), and glycogen synthase decreased (P less than 0.001) during UHE. It is concluded that E inhibits insulin-mediated glycogenesis because of an inactivation of glycogen synthase and an activation of glycogenolysis. E also appears to inhibit insulin-mediated glucose utilization, at least partly, because of an increase in G-6-phosphate (which inhibits hexokinase) and enhances glycolysis by G-1,6-P2-, fructose 6-phosphate-, and F-1,6-P2-mediated activation of PFK.
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Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016.
Katz
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Spencer
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D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D006005:Phosphorylases / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D006003:Glycogen; D006005:Phosphorylases; D006006:Glycogen Synthase; D009638:Norepinephrine; D004837:Epinephrine