Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration
Effect of acute and recurrent hypoglycemia on changes in brain glycogen concentration
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DOI：
10.1210/en.2007-1252
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发表时间：
2008-04-01
期刊：
影响因子：
4.8
通讯作者：
Sherwin, Robert S.
中科院分区：
文献类型：
--
作者：
Herzog, Raimund I.;Chan, Owen;Sherwin, Robert S.
我们的目的是评估是否过量的脑糖原沉积可能遵循急性低血糖（AH）发作，从而在接受强化胰岛素治疗的糖尿病患者中观察到的低血糖相关自主神经功能衰竭中发挥作用。我们确定了AH和反复低血糖（RH）后的脑葡萄糖和糖原恢复动力学，这是一个建立的反调节失败的动物模型。连续3天的单次胰岛素诱导的AH或RH用于消耗大鼠脑葡萄糖和糖原储备。在微波固定和糖原提取后，使用生物化学测定法测定脑中的区域恢复动力学。AH和RH处理均使小脑、皮质和下丘脑中的糖原水平分别从对照水平7.78 +/- 0.55、5.4 +/- 0.38和4.45 +/- 0.37 μ mol/g降低至约50%，对应于0.6和1.2 μ mol/g. h之间的净糖原利用率。低血糖后，AH组和RH组的糖原水平均在6小时内恢复至基线水平。然而，在暴露于RH的大鼠中，脑糖原的恢复往往更快。这一效应是在RH组脑葡萄糖水平恢复更快之后出现的，尽管两组的血糖水平相似。两组中的糖原水平均未出现高于基线的统计学显著性增加。特别是，脑糖原没有增加后24小时，最后一次反复发作的低血糖，当一个显着的反调节缺陷，可以记录在一个高胰岛素低血糖钳夹研究。我们的结论是，糖原超代偿不是一个主要的贡献因素的发病机制，低血糖相关的自主神经功能衰竭。
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 mu mol/g, respectively, to approximately 50% corresponding to a net glycogen utilization rate between 0.6 and 1.2 mu mol/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.