绵羊和兔子的脑葡萄糖转运与氧消耗

Cerebral glucose transport and oxygen consumption in sheep and rabbits.

作者信息

Pappenheimer J R, Setchell B P

出版信息

J Physiol. 1973 Sep;233(3):529-51. doi: 10.1113/jphysiol.1973.sp010322.

DOI:10.1113/jphysiol.1973.sp010322

PMID:4754872

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1350591/

Abstract

Mechanisms underlying the ability of ruminants to tolerate severe hypoglycaemia have been investigated. Anaesthetized sheep and rabbits were compared with respect to cerebral glucose transport and oxygen consumption as a function of glucose concentration in cerebral extracellular fluids.2. Glucose in plasma was decreased by insulin or increased by I.V. infusion. Measurements were made of cerebral blood flow, arteriovenous concentration differences of glucose and oxygen and the concentration of glucose in c.s.f.3. Equations for carrier-mediated transport accurately described steady-state glucose flux across the blood-brain barrier as plasma concentration was varied from 0.2 to 30 mM. In sheep, the affinity constant (K(m)) was 6 mM and the maximum transport capacity (T(m)) was 260 mumole min(-1). 100 g(1) brain. In rabbits, K(m) = 5.5 mM and T(m) = 280 mumole min(-1). 100 g(1). Transport of glucose across the blood-brain barrier of rabbits is at least as efficient as that in sheep and in both species T(m) is 10-15 times greater than normal rates of glucose utilization.4. During hypoglycaemia the concentration of glucose in c.s.f. is less in sheep than in rabbits (Fig. 5). Steady-state utilization of glucose by sheep brain decreased to 50% of normal when steady-state concentration of glucose in c.s.f. (interstitial fluid) falls to 0.1 mumole ml.(-1); in rabbits the corresponding concentration is 0.7 mumole ml.(-1) (Fig. 6). We suggest that transport capacity of membranes separating cerebral interstitial fluid from the site of glucose phosphorylation is greater in sheep than in rabbits; this may be the principal adaptation which enables ruminants to withstand severe hypoglycaemia (Discussion II).5. Approximately 30 min were required to reach a steady state of glucose transport following a sudden increment of glucose concentration in plasma (Fig. 1). 80-100 min were required to reach a new steady-state concentration of glucose in c.s.f.6. The molar ratio of steady-state cerebral glucose utilization to oxygen consumption (6G:O(2)) is normally 0.93 (S.E. +/- 0.05) but is decreased to the range 0.1-0.5 during sustained hypoglycaemia in both sheep and rabbits (Figs. 2, 3). Continued low glucose: oxygen ratios could be explained by (a) utilization of non-carbohydrate substrates derived from blood or (b) utilization of stored lipid in brain. Only 0.1 g lipid/100 g brain would suffice to account for the observed rate of non-glucose oxidative metabolism during 3 hr of severe hypoglycaemia (Discussion IV).

摘要

对反刍动物耐受严重低血糖能力的潜在机制进行了研究。将麻醉的绵羊和兔子在脑葡萄糖转运和氧消耗方面进行比较，作为脑细胞外液中葡萄糖浓度的函数。
通过胰岛素降低血浆中的葡萄糖或通过静脉输注增加葡萄糖。测量脑血流量、葡萄糖和氧的动静脉浓度差以及脑脊液中葡萄糖的浓度。
当血浆浓度从0.2 mM变化到30 mM时，载体介导转运的方程准确描述了跨血脑屏障的稳态葡萄糖通量。在绵羊中，亲和常数（K(m)）为6 mM，最大转运能力（T(m)）为260微摩尔·分钟⁻¹·100克⁻¹脑。在兔子中，K(m) = 5.5 mM，T(m) = 280微摩尔·分钟⁻¹·100克⁻¹。葡萄糖跨兔子血脑屏障的转运效率至少与绵羊相同，并且在两个物种中T(m)都比正常葡萄糖利用速率大10 - 15倍。
在低血糖期间，绵羊脑脊液中的葡萄糖浓度低于兔子（图5）。当脑脊液（间质液）中葡萄糖的稳态浓度降至0.1微摩尔·毫升⁻¹时，绵羊脑葡萄糖的稳态利用率降至正常的50%；在兔子中，相应浓度为0.7微摩尔·毫升⁻¹（图6）。我们认为，将脑细胞间质液与葡萄糖磷酸化部位分隔开的膜的转运能力在绵羊中比在兔子中更大；这可能是使反刍动物能够耐受严重低血糖的主要适应性变化（讨论II）。
血浆中葡萄糖浓度突然增加后，大约需要30分钟才能达到葡萄糖转运的稳态（图1）。需要80 - 100分钟才能在脑脊液中达到新的葡萄糖稳态浓度。
稳态脑葡萄糖利用率与氧消耗的摩尔比（6G:O₂）通常为0.93（标准误±0.05），但在绵羊和兔子持续低血糖期间降至0.1 - 0.5的范围（图2、3）。持续的低葡萄糖:氧比值可以用以下两种情况解释：(a) 利用来自血液的非碳水化合物底物或(b) 利用脑中储存的脂质。在严重低血糖3小时期间，仅0.1克脂质/100克脑就足以解释观察到的非葡萄糖氧化代谢速率（讨论IV）。