Blazey Tyler, Lee John J, Snyder Abraham Z, Goyal Manu S, Hershey Tamara, Arbeláez Ana Maria, Raichle Marcus E
Mallinckrodt Institute of Radiology, School of Medicine, Washington University, St. Louis, MO, USA.
Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA.
J Cereb Blood Flow Metab. 2025 Jul 1:271678X251329714. doi: 10.1177/0271678X251329714.
Multiple studies have shown that hyperglycemia increases the cerebral metabolic rate of glucose (CMRglc) in subcortical white matter. This observation remains unexplained. Using positron emission tomography (PET) and pancreatic glucose clamps with basal insulin replacement in twenty-nine healthy young adults (34.5 years, SD = 10.1) we found that acute hyperglycemia increases non-oxidative CMRglc (i.e., aerobic glycolysis (AG)) in subcortical white mater as well as in medial temporal lobe structures, cerebellum and brainstem, all areas with low CMRglc during euglycemia. Surprisingly, hyperglycemia did not change regional cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO), or the blood-oxygen-level-dependent (BOLD) response. Correlation with existing regional gene expression data showed that brain regions where CMRglc increased have greater expression of hexokinase 2 (). Simulations of glucose transport revealed that, unlike hexokinase 1, is not saturated at euglycemia, and thus can accommodate increased AG during hyperglycemia.
多项研究表明，高血糖会增加皮质下白质的脑葡萄糖代谢率（CMRglc）。这一观察结果仍无法解释。我们对29名健康的年轻成年人（34.5岁，标准差=10.1）进行正电子发射断层扫描（PET）和基础胰岛素替代的胰腺葡萄糖钳夹实验，发现急性高血糖会增加皮质下白质以及内侧颞叶结构、小脑和脑干的非氧化CMRglc（即有氧糖酵解（AG）），这些区域在血糖正常时CMRglc较低。令人惊讶的是，高血糖并未改变局部脑血流量（CBF）、脑氧代谢率（CMRO）或血氧水平依赖（BOLD）反应。与现有局部基因表达数据的相关性表明，CMRglc增加的脑区己糖激酶2（）的表达更高。葡萄糖转运模拟显示，与己糖激酶1不同，在血糖正常时不饱和，因此在高血糖期间可以适应增加的AG。
