INVITRO STUDIES OF THE SUBSTRATES FOR ENERGY-PRODUCTION AND THE EFFECTS OF INSULIN ON GLUCOSE-UTILIZATION IN THE NEURAL COMPONENTS OF PERIPHERAL-NERVE
INVITRO STUDIES OF THE SUBSTRATES FOR ENERGY-PRODUCTION AND THE EFFECTS OF INSULIN ON GLUCOSE-UTILIZATION IN THE NEURAL COMPONENTS OF PERIPHERAL-NERVE
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DOI：
10.2337/diabetes.28.10.878
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发表时间：
1979-01-01
期刊：
影响因子：
7.7
通讯作者：
WINEGRAD, AI
中科院分区：
文献类型：
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作者：
GREENE, DA;WINEGRAD, AI
利用兔胫神经束神经内膜制备物，研究了周围神经轴突和雪旺细胞从葡萄糖D- β中获取复合能量需求的能力。-羟基丁酸酯或白蛋白结合棕榈酸酯，以及胰岛素对其体外复合葡萄糖利用的影响。样品与5 mM葡萄糖孵育2小时，保持稳定的氧摄取、p -肌酸和ATP浓度，p -肌酸/肌酸比值略有增加（制备的EM外观在这些条件下未发生变化）。葡萄糖氧化所需的氧气摄取速率占葡萄糖摄取的61%。在无底物孵育2小时的样品中，组织葡萄糖的显著下降与50%的氧气摄取减少以及p -肌酸、ATP和p -肌酸/肌酸比值的减少有关。培养基中不含葡萄糖，但含有5mmdl - β。-羟基丁酸，稳定的D- β速率。观察到-羟基丁酸摄取，乙酰乙酸仅占一小部分；虽然p -肌酸和p -肌酸/肌酸比值下降，但仍显著高于无底物孵育后的水平。已知存在一种有效的白蛋白血-神经屏障。含有白蛋白结合棕榈酸盐的培养基，棕榈酸/白蛋白的摩尔比为1或2 (FFA[游离脂肪酸]的最高浓度为1.32 meq/l)，在无葡萄糖的孵育过程中未能防止p -肌酸、ATP和p -肌酸/肌酸比值的下降；相关的氧摄取表明，与非神经组织相比，暴露于白蛋白结合棕榈酸盐的组织易受呼吸解耦和抑制。胰岛素（100或1000 .亩）U[单位]/ml)与5 mM葡萄糖或（U[均匀标记]-14C）葡萄糖孵育2小时，对神经内膜制剂中葡萄糖的利用没有可检测到的影响。在兔坐骨神经外神经组织中，胰岛素(100 .mu。U/ml)增加了（U- 14c）葡萄糖向CO2和总脂质的掺入。在大多数不存在血浆酮体浓度升高的生理条件下，周围神经的神经成分可能依赖葡萄糖作为能量产生和呼吸的主要底物；它们的复合葡萄糖利用不受胰岛素浓度的急性、直接调节，而胰岛素浓度可能合理地来自于胰腺源的血浆胰岛素。
An endoneurial preparation from a rabbit tibial nerve fascicle was used to study the ability of peripheral nerve axons and Schwann cells to derive their composite energy requirements from glucose, D-.beta.-hydroxybutyrate, or albumin-bound palmitate, and the effects of insulin in vitro on their composite glucose utilization. Samples incubated with 5 mM glucose for 2 h maintained a stable O2 uptake and P-creatine and ATP concentrations, and they exhibited a slight increase in P-creatine/creatine ratio (the EM appearance of the preparation was previously shown to be unaltered under these conditions). The rate of glucose oxidation required to account for the O2 uptake accounted for 61% of the glucose uptake. In samples incubated without substrate for 2 h, a marked fall in tissue glucose was associated with a 50% decrease in O2 uptake and with decreases in P-creatine, ATP and in the P-creatine/creatine ratio. In medium lacking glucose but containing 5 mM DL-.beta.-hydroxybutyrate, a stable rate of D-.beta.-hydroxybutyrate uptake was observed, and acetoacetate production accounted for only a small fraction; significant decreases in O2 uptake or ATP were prevented, and, although P-creatine and the P-creatine/creatine ratio fell, they remained significantly higher than after incubation without substrate. An efficient blood-nerve barrier to albumin is known to exist. Medium containing albumin-bound palmitate with molar ratios of palmitate/albumin of 1 or 2 (highest FFA [free fatty acid] concentration, 1.32 meq/l) failed to prevent decreases in P-creatine, ATP and in the P-creatine/creatine ratio during incubations without glucose; the associated O2 uptakes suggested that the tissue is susceptible to respiratory uncoupling and depression on exposure to albumin-bound palmitate as compared with non-neural tissue. Insulin (100 or 1000 .mu.U[units]/ml) had no detectable effects on glucose utilization in the endoneurial preparation during 2 h incubations with 5 mM glucose or (U[uniformly labeled]-14C) glucose. In contrast, in epineurial tissue from rabbit sciatic nerve, insulin (100 .mu.U/ml) increased (U-14C) glucose incorporation into CO2 and total lipid. The neural components of peripheral nerve are probably dependent on glucose as their major substrate for energy production and respiration under most physiologic conditions in which elevated plasma ketone body concentrations are absent; their composite glucose utilization is not subject to acute, direct regulation by insulin in concentrations that might reasonably be derived from plasma insulin of pancreatic origin.