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乳酸可逆转哺乳-断奶期小鼠胰岛素诱导的低血糖昏迷:血液、肝脏和大脑中的生化关联

Lactate reverses insulin-induced hypoglycemic stupor in suckling-weanling mice: biochemical correlates in blood, liver, and brain.

作者信息

Thurston J H, Hauhart R E, Schiro J A

出版信息

J Cereb Blood Flow Metab. 1983 Dec;3(4):498-506. doi: 10.1038/jcbfm.1983.77.

DOI:10.1038/jcbfm.1983.77
PMID:6313715
Abstract

The recovery of weanling mice from insulin-induced hypoglycemic stupor-coma after injection of sodium -L(+)-lactate (18 mmol/kg) was as rapid (10 min) as in litter-mates treated with glucose (9 mmol/kg). Stimulated by this dramatic action, we studied the effects of lactate injection on brain carbohydrate and energy metabolism in normal and hypoglycemic mice; blood and liver tissue were also studied. Ten minutes after lactate injection in normal mice, plasma lactate levels increased by 15 mmol/L; plasma glucose levels were unchanged, but the beta-hydroxybutyrate concentration fell 59%. In the brains of these animals, glucose levels increased 2.3-fold, and there were significant increases in brain glycogen (10%), glucose-6-phosphate (27%), lactate (68%), pyruvate (37%), citrate (12%), and malate (19%); the increase in alpha-ketoglutarate (32%) was not significant. Lactate injection reduced the cerebral glucose-use rate 40%. These changes were not due to lactate-induced increases in blood [HCO-3] and pH (examined by injection of 15 mmol/kg sodium bicarbonate). Although lactate injection of hypoglycemic mice doubled levels of glucose in plasma and brain (not significant) and most of the cerebral glycolytic intermediates, values were far below normal (still in the range seen in hypoglycemic animals). By contrast, citrate and alpha-ketoglutarate levels returned to normal; the large increase in malate was not significant. Reduced glutamate levels increased to normal, and elevated aspartate levels fell below normal. Thus, recovery from hypoglycemic stupor does not necessarily depend on normal levels of plasma and/or brain glucose (or glycolytic intermediates).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

给断乳小鼠注射胰岛素诱导低血糖昏迷后,注射L(+)-乳酸钠(18 mmol/kg),其从低血糖昏迷中苏醒的速度(10分钟)与注射葡萄糖(9 mmol/kg)的同窝小鼠一样快。受此显著作用的刺激,我们研究了注射乳酸对正常和低血糖小鼠脑碳水化合物及能量代谢的影响;同时也研究了血液和肝脏组织。正常小鼠注射乳酸10分钟后,血浆乳酸水平升高15 mmol/L;血浆葡萄糖水平未变,但β-羟基丁酸浓度下降了59%。在这些动物的脑中,葡萄糖水平增加了2.3倍,脑糖原(10%)、6-磷酸葡萄糖(27%)、乳酸(68%)、丙酮酸(37%)、柠檬酸(12%)和苹果酸(19%)均显著增加;α-酮戊二酸增加(32%)不显著。注射乳酸使脑葡萄糖利用率降低40%。这些变化并非由于乳酸诱导血液中[HCO₃⁻]和pH值升高(通过注射15 mmol/kg碳酸氢钠进行检测)。尽管给低血糖小鼠注射乳酸后,血浆和脑中的葡萄糖水平(不显著)以及大多数脑糖酵解中间产物增加了一倍,但数值仍远低于正常水平(仍处于低血糖动物所见范围内)。相比之下,柠檬酸和α-酮戊二酸水平恢复正常;苹果酸的大幅增加不显著。降低的谷氨酸水平升至正常,升高的天冬氨酸水平降至正常水平以下。因此,从低血糖昏迷中恢复不一定依赖于血浆和/或脑葡萄糖(或糖酵解中间产物)的正常水平。(摘要截断于250字)

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Beta-hydroxybutyrate reverses insulin-induced hypoglycemic coma in suckling-weanling mice despite low blood and brain glucose levels.尽管血糖和脑葡萄糖水平较低,但β-羟基丁酸可逆转胰岛素诱导的乳鼠至断奶期小鼠的低血糖昏迷。
Metab Brain Dis. 1986 Mar;1(1):63-82. doi: 10.1007/BF00998478.
6
Effect of momentary stress on brain energy metabolism in weanling mice: apparent use of lactate as cerebral metabolic fuel concomitant with a decrease in brain glucose utilization.短暂应激对断奶小鼠脑能量代谢的影响:乳酸作为脑代谢燃料的明显利用伴随着脑葡萄糖利用的减少。
Metab Brain Dis. 1989 Sep;4(3):177-86. doi: 10.1007/BF01000294.