A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover

A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover
复制标题

DOI:
10.1111/j.1471-4159.2007.04595.x
复制
发表时间:
2007-07-01
影响因子:
4.7
通讯作者:
Cruz, Nancy F.
Cruz, Nancy F.
中科院分区:
医学2区
文献类型:
--
作者:
Dienel, Gerald A.;Ball, Kelly K.;Cruz, Nancy F.

文献摘要

被引文献

相似文献

糖原在脑活动过程中降解,但其在正常脑活动中的作用和对功能能量的贡献尚未确定。本研究通过糖原磷酸化酶抑制剂治疗引起的糖原浓度变化、预标记糖原释放的C-14和代偿性血糖利用增加(CMRglc)三种方法来评估正常意识大鼠在感觉刺激时的脑糖原利用。皮质糖原水平下降,三个结构中C-14释放增加,抑制剂处理导致CMRglc的区域选择性代偿性增加,高于激活诱导的大鼠。CMRglc代偿性升高在感觉顶叶皮层最高,约占刺激诱导的CMRglcf升高的一半;这种反应与代谢率、刺激诱导的CMRglc升高或感觉通路的顺序站无关。因此,在正常激活的大脑中,糖原是特定结构的活性燃料,而不仅仅是一个应急燃料库,在激活过程中,通量产生的丙酮酸大大超过乳酸的净积累或糖原的净消耗。糖原的代谢命运尚不清楚,但在激活过程中消耗的燃料中添加糖原会导致cmr2 /CMRglc比率下降。
Glycogen is degraded during brain activation but its role and contribution to functional energetics in normal activated brain have not been established. In the present study, glycogen utilization in brain of normal conscious rats during sensory stimulation was assessed by three approaches, change in concentration, release of C-14 from pre-labeled glycogen and compensatory increase in utilization of blood glucose (CMRglc) evoked by treatment with a glycogen phosphorylase inhibitor. Glycogen level fell in cortex, C-14 release increased in three structures and inhibitor treatment caused regionally selective compensatory increases in CMRglc over and above the activation-induced rise in vehicle-treated rats. The compensatory rise in CMRglc was highest in sensory-parietal cortex where it corresponded to about half of the stimulus-induced rise in CMRglcf in vehicle-treated rats; this response did not correlate with metabolic rate, stimulus-induced rise in CMRglc or sequential station in sensory pathway. Thus, glycogen is an active fuel for specific structures in normal activated brain, not simply an emergency fuel depot and flux-generated pyruvate greatly exceeded net accumulation of lactate or net consumption of glycogen during activation. The metabolic fate of glycogen is unknown, but adding glycogen to the fuel consumed during activation would contribute to a fall in CMRO2/CMRglc ratio.