NMR measurements of in vivo myocardial glycogen metabolism.
Using 13C and 1H NMR we measured the rate of glycogen synthesis (0.23 +/- 0.10 mumol/min gram wet weight tissue (gww) in rat heart in vivo during an intravenous infusion of D-[1-13C]glucose and insulin. Glycogen was observed within 10 min of starting and increased linearly throughout a 50-min infusion. This compared closely with the average activity of glycogen synthase I (0.22 +/- 0.03 mumol/min gww) measured at physiologic concentrations of UDP-glucose (92 microM) and glucose-6-phosphate (110 microM). When unlabeled glycogen replaced D-[1-13C]glucose in the infusate after 50 min the D-[1-13C]glycogen signal remained stable for another 60 min, indicating that no turnover of the newly synthesized glycogen had occurred. Despite this phosphorylase a activity in heart extracts from rats given a 1 h glucose and insulin infusion (3.8 +/- 2.4 mumol/min gww) greatly exceeded the total synthase activity and if active in vivo should promote glycogenolysis. We conclude that during glucose and insulin infusion in the rat: (a) the absolute rate of myocardial glycogen synthesis can be measured in vivo by NMR; (b) glycogen synthase I can account for the observed rates of heart glycogen synthesis; (c) there is no futile cycling of glucose in and out of heart glycogen; and (d) the activity of phosphorylase a measured in tissue extracts is not reflected in vivo. These studies raise the question whether significant regulation of phosphorylase a activity in vivo is mediated by factors in addition to its phosphorylation state.
D000465:Algorithms; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen; D006005:Phosphorylases; D006006:Glycogen Synthase