Human Brain Glycogen Metabolism During and After Hypoglycemia

Human Brain Glycogen Metabolism During and After Hypoglycemia Gülin Öz 1 , Anjali Kumar 2 , Jyothi P. Rao 2 , Christopher T. Kodl 2 , Lisa Chow 2 , Lynn E. Eberly 3 and Elizabeth R. Seaquist 2 1 Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota; 2 Department of Medicine, Medical School, University of Minnesota, Minneapolis, Minnesota; 3 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota. Corresponding author: Gülin Öz, gulin{at}cmrr.umn.edu . Abstract OBJECTIVE We tested the hypotheses that human brain glycogen is mobilized during hypoglycemia and its content increases above normal levels (“supercompensates”) after hypoglycemia. RESEARCH DESIGN AND METHODS We utilized in vivo 13 C nuclear magnetic resonance spectroscopy in conjunction with intravenous infusions of [ 13 C]glucose in healthy volunteers to measure brain glycogen metabolism during and after euglycemic and hypoglycemic clamps. RESULTS After an overnight intravenous infusion of 99% enriched [1- 13 C]glucose to prelabel glycogen, the rate of label wash-out from [1- 13 C]glycogen was higher (0.12 ± 0.05 vs. 0.03 ± 0.06 μmol · g −1 · h −1 , means ± SD, P < 0.02, n = 5) during a 2-h hyperinsulinemic-hypoglycemic clamp (glucose concentration 57.2 ± 9.7 mg/dl) than during a hyperinsulinemic-euglycemic clamp (95.3 ± 3.3 mg/dl), indicating mobilization of glucose units from glycogen during moderate hypoglycemia. Five additional healthy volunteers received intravenous 25–50% enriched [1- 13 C]glucose over 22–54 h after undergoing hyperinsulinemic-euglycemic (glucose concentration 92.4 ± 2.3 mg/dl) and hyperinsulinemic-hypoglycemic (52.9 ± 4.8 mg/dl) clamps separated by at least 1 month. Levels of newly synthesized glycogen measured from 4 to 80 h were higher after hypoglycemia than after euglycemia ( P ≤ 0.01 for each subject), indicating increased brain glycogen synthesis after moderate hypoglycemia. CONCLUSIONS These data indicate that brain glycogen supports energy metabolism when glucose supply from the blood is inadequate and that its levels rebound to levels higher than normal after a single episode of moderate hypoglycemia in humans. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received February 16