Our objective was to evaluate whether excessive brain
glycogen deposition might follow episodes of acute
hypoglycemia (AH) and thus play a role in the
hypoglycemia-associated autonomic failure seen in diabetic patients receiving intensive
insulin treatment. We determined brain
glucose and
glycogen recovery kinetics after AH and recurrent
hypoglycemia (RH), an established animal model of counterregulatory failure. A single bout of
insulin-induced AH or RH for 3 consecutive days was used to deplete brain
glucose and
glycogen stores in rats. After microwave fixation and
glycogen extraction, regional recovery kinetics in the brain was determined using a biochemical assay. Both AH and RH treatments reduced
glycogen levels in the cerebellum, cortex, and hypothalamus from control levels of 7.78 +/- 0.55, 5.4 +/- 0.38, and 4.45 +/- 0.37 micromol/g, respectively, to approximately 50% corresponding to a net
glycogen utilization rate between 0.6 and 1.2 micromol/g.h. After
hypoglycemia,
glycogen levels returned to baseline within 6 h in both the AH and the RH group. However, recovery of brain
glycogen tended to be faster in rats exposed to RH. This effect followed more rapid recovery of brain
glucose levels in the RH group, despite similar
blood glucose levels in both groups. There was no statistically significant increase above baseline
glycogen levels in either group. In particular, brain
glycogen was not increased 24 h after the last of recurrent episodes of
hypoglycemia, when a significant counterregulatory defect could be documented during a hyperinsulinemic
hypoglycemic clamp study. We conclude that
glycogen supercompensation is not a major contributory factor to the pathogenesis of
hypoglycemia-associated autonomic failure.