Orzi F, Lucignani G, Dow-Edwards D, Namba H, Nehlig A, Patlak C S, Pettigrew K, Schuier F, Sokoloff L
Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892.
J Cereb Blood Flow Metab. 1988 Jun;8(3):346-56. doi: 10.1038/jcbfm.1988.70.
Local cerebral glucose utilization assayed by the [14C]deoxyglucose ([14C]DG) method and calculated by means of its operational equation with values for the rate constants and lumped constant determined in rats under physiological conditions remains relatively stable with variations in arterial plasma glucose concentration within the normoglycemic range. Large changes in arterial plasma glucose level may, however, significantly alter the values of these constants and lead to artifactual results. Values for the lumped constant have been measured and reported for a wide range of arterial plasma glucose concentrations ranging from hypoglycemia to hyperglycemia in the rat (Schuier et al., 1981; Suda et al., 1981; Pettigrew et al., 1983). In the present study we have redetermined the rate constants in rats with arterial plasma glucose levels clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM) by a glucose clamp technique. The rate constants for the transport of DG from plasma to brain, K1*, and its phosphorylation in tissue, k3*, were found to decline with increasing plasma glucose levels, while the rate constant for its transport back from brain to plasma, k*2, remained relatively unchanged from its value in normoglycemia. These rate constants were used together with the previously determined values for the lumped constants to calculate local rates of cerebral glucose utilization in three groups of rats in which arterial plasma glucose levels were clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM). Average glucose utilization in the brain as a whole was unchanged in hyperglycemia from the values calculated in normoglycemic rats with the standard normal set of constants. Changes in the rate of glucose utilization were found, however, in the hypothalamus, globus pallidus, and amygdala during hyperglycemia.
采用[¹⁴C]脱氧葡萄糖（[¹⁴C]DG）法测定并通过其运算方程计算的局部脑葡萄糖利用率，其速率常数和集总常数的值是在大鼠生理条件下测定的，在正常血糖范围内，随着动脉血浆葡萄糖浓度的变化，该利用率仍相对稳定。然而，动脉血浆葡萄糖水平的大幅变化可能会显著改变这些常数的值，并导致人为的结果。在大鼠中，已测量并报告了从低血糖到高血糖的广泛动脉血浆葡萄糖浓度范围内的集总常数的值（Schuier等人，1981年；Suda等人，1981年；Pettigrew等人，1983年）。在本研究中，我们通过葡萄糖钳夹技术重新测定了动脉血浆葡萄糖水平钳夹在约350、450和550mg/dl（即19、25和31mM）的大鼠的速率常数。发现DG从血浆转运到脑的速率常数K1及其在组织中的磷酸化速率常数k3随着血浆葡萄糖水平的升高而下降，而其从脑转运回血浆的速率常数k*2与正常血糖时的值相比相对不变。这些速率常数与先前测定的集总常数的值一起用于计算三组大鼠的局部脑葡萄糖利用率，这三组大鼠的动脉血浆葡萄糖水平分别钳夹在约350、450和550mg/dl（即19、25和31mM）。与使用标准正常常数集在正常血糖大鼠中计算的值相比，高血糖时整个大脑的平均葡萄糖利用率没有变化。然而，在高血糖期间，下丘脑、苍白球和杏仁核的葡萄糖利用率发生了变化。
