Abstract

Objective: We tested the hypotheses that human brain glycogen is mobilized during hypoglycemia and its content increases above normal levels (“supercompensates”) following hypoglycemia.

Research Design and Methods: We utilized in vivo ¹³C NMR spectroscopy in conjunction with IV infusions of ¹³C-glucose in healthy volunteers to measure brain glycogen metabolism during and following euglycemic and hypoglycemic clamps.

Results: Following an overnight IV infusion of 99% enriched [1-¹³C]glucose to pre-label glycogen, the rate of label wash-out from [1-¹³C]glycogen was higher (0.12 ± 0.05 vs. 0.03 ± 0.06 μmol/g/h, mean ± SD, p < 0.02, N = 5) during a 2 hour 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 IV 25-50% enriched [1-¹³C]glucose over 22 - 54 hours after undergoing hyperinsulinemic/euglycemic (glucose concentration 92.4 ± 2.3 mg/dl) and hyperinsulinemic/hypoglycemic clamps (52.9 ± 4.8 mg/dl) separated by at least one month. Levels of newly synthesized glycogen measured from 4 - 80 hours 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 following a single episode of moderate hypoglycemia in humans.