Duarte João M N, Morgenthaler Florence D, Gruetter Rolf
Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 6, 1015, Lausanne, Switzerland.
Cellular Imaging Facility, University of Lausanne, Lausanne, Switzerland.
Neurochem Res. 2017 Jun;42(6):1629-1635. doi: 10.1007/s11064-017-2178-z. Epub 2017 Jan 12.
Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.
糖尿病患者对低血糖的生理性反调节反应会逐渐衰退，导致低血糖无意识症。大脑适应低血糖的机制可能涉及脑糖原。我们检验了这样一个假设，即低血糖后大脑糖原的超补偿取决于恢复期间的血糖水平。将清醒的大鼠置于2毫摩尔/升的低血糖状态90分钟，然后通过静脉输注葡萄糖使其在不同血糖水平下恢复。恢复24小时后，大脑皮层、海马体和纹状体中的脑糖原浓度升高至对照水平以上。这种糖原超补偿与低血糖后时期的血糖水平无关。在没有先前低血糖损伤的情况下，高血糖状态下24小时后脑糖原浓度未发生改变。在下丘脑，即控制外周葡萄糖稳态的部位，糖原水平未发生改变。总体而言，我们得出结论，低血糖后糖原超补偿发生在几个脑区，其程度与血浆葡萄糖水平无关。通过在反复低血糖期间支持大脑代谢，糖原可能在低血糖无意识症的发展中起作用。
