AIM AND OBJECTIVE Insulin-induced moderate or severe hypoglycemia (MH or SH) impairs cognition and SH causes neuronal death. On the contrary, alternate day fasting (ADF) protects the brain during excitotoxic stress and improves cognitive function. Unlike the scenario in the periphery, insulin and its relationship towards brain glucose uptake and metabolism are considered to be less significant. Yet, the hypoglycemia associated brain metabolism is not clearly understood. The authors broadly investigated the brain metabolism in various hypoglycemic models such as insulin-induced MH, SH, SH with glucose reperfusion, 24 h fasting and ADF in the cortex or hippocampus of C57BL6/J mice. The authors analyzed the protein expression of insulin signaling kinases (plays a key role in neuronal survival and memory), Bcl-2 associated death promoter (p-BADser155) (dephosphorylation inhibits glucokinase activity and reduces glucose or increases ketone body metabolism in the brain), neuronal-specific glucose transporter 3 (GLUT 3) and nitrotyrosine (marker of nitric oxide which is involved in neuronal glucose uptake via GLUT 3) using western blotting analysis. RESULTS Insulin-induced MH or SH differentially regulated the brain insulin signaling kinases. The expression of p-BADser155 decreased in all hypoglycemic models except the insulin-induced MH in hippocampus. The trended higher GLUT 3 and increased nitrotyrosine expression of insulin-induced SH were restored after glucose reperfusion. The trended higher or increased GLUT 3 and nitrotyrosine expression of ADF were positively correlated with serum beta-hydroxybutyrate levels. CONCLUSION During hypoglycemia, it can be suggested that the brain might decrease glucose metabolism via glycolysis or prefer ketone body metabolism (except the insulin-induced MH in hippocampus) by modifying the p-BADser155 expression. In addition to the ketone body metabolism, the brain might adapt to uptake glucose in insulin-induced SH or ADF by modifying the GLUT 3 or nitrotyrosine expression.

中文翻译：

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小鼠各种降血糖模型中胰岛素信号激酶，GLUT 3，p-BADser155和硝基酪氨酸表达的大脑适应性。

目的和目的胰岛素引起的中度或重度低血糖症（MH或SH）损害认知，SH导致神经元死亡。相反，隔日禁食（ADF）在兴奋性中毒压力下保护大脑并改善认知功能。与周围环境不同，胰岛素及其与脑葡萄糖摄取和代谢的关系被认为不那么重要。然而，与低血糖有关的脑代谢尚不清楚。作者广泛研究了各种低血糖模型的脑代谢，例如C57BL6 / J小鼠皮质或海马中的胰岛素诱导的MH，SH，SH以及葡萄糖再灌注，24小时禁食和ADF。作者分析了胰岛素信号激酶的蛋白表达（在神经元存活和记忆中起关键作用），Bcl-2相关死亡促进剂（p-BADser155）（去磷酸化抑制葡萄糖激酶活性并降低大脑中的葡萄糖或增加酮体的新陈代谢），神经元特异性葡萄糖转运蛋白3（GLUT 3）和硝基酪氨酸（一氧化氮的标志物通过蛋白质印迹分析，通过GLUT 3）摄取神经元葡萄糖。结果胰岛素诱导的MH或SH差异性调节脑胰岛素信号激酶。在所有降血糖模型中，p-BADser155的表达均下降，除了胰岛素诱导的海马体MH以外。葡萄糖再灌注后，恢复了胰岛素诱导的SH的趋势，即更高的GLUT 3和增加的硝基酪氨酸表达。ADF的GLUT 3和硝基酪氨酸表达的升高或升高趋势与血清β-羟基丁酸酯水平呈正相关。结论在低血糖期间，可能提示大脑可能通过修饰p-BADser155表达而通过糖酵解降低葡萄糖代谢，或偏向酮体代谢（胰岛素诱导的海马MH除外）。除了酮体代谢外，大脑还可能通过修饰GLUT 3或硝基酪氨酸表达来适应胰岛素诱导的SH或ADF中的葡萄糖摄取。