Cerebral glucose transport and oxygen consumption in sheep and rabbits.

1. 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).