Stevens M J, Lattimer S A, Kamijo M, Van Huysen C, Sima A A, Greene D A
Department of Internal Medicine, University of Michigan, Ann Arbor.
Diabetologia. 1993 Jul;36(7):608-14. doi: 10.1007/BF00404069.
Diabetic neuropathy results from progressive nerve fibre damage with blunted nerve regeneration and repair and may be complicated by nerve hyperexcitability resulting in pain. The naturally occurring amino acid taurine functions as an osmolyte, inhibitory neurotransmitter, and modulator of pain perception. It is also known to have neurotrophic actions. The compatible osmolyte hypothesis proposes that levels of intracellular organic osmolytes including taurine and myo-inositol, respond co-ordinately in response to changes in intracellular sorbitol or external osmolality to maintain the intracellular milieu. We hypothesize that glucose-induced sorbitol accumulation in diabetes mellitus will result in taurine depletion in peripheral nerve which may potentially impair nerve regeneration and precipitate neuronal hyperexcitability and pain. This study explored the relationships of taurine, myo-inositol and sorbitol in the rat nerve and their effects on nerve conduction velocity. Osmolyte levels and nerve conduction velocity were determined in sciatic nerve from non-diabetic and streptozotocin-induced diabetic rats, with or without dietary taurine or myo-inositol supplementation. Taurine levels decreased by 31% (p < 0.01) and myo-inositol decreased by 37% (p < 0.05) in diabetic nerve as sorbitol accumulated. Taurine supplementation of diabetic animals did not affect nerve conduction velocity but further reduced nerve myo-inositol levels. Prevention of sorbitol accumulation with the aldose reductase inhibitor sorbinil increased nerve taurine levels by 22% (p < 0.05) when compared with untreated diabetic animals. Thus, we have demonstrated an interdependence of organic osmolytes within the nerve. Abnormal accumulation of one osmolyte results in reciprocal depletion of others. Diabetic neuropathy may be an example of maladaptive osmoregulation, nerve damage and instability being aggravated by taurine depletion.
糖尿病性神经病变是由神经纤维进行性损伤、神经再生和修复受阻所致，可能并发神经兴奋性增高而产生疼痛。天然存在的氨基酸牛磺酸具有渗透溶质、抑制性神经递质以及痛觉感知调节剂的作用。已知它还具有神经营养作用。相容性渗透溶质假说提出，包括牛磺酸和肌醇在内的细胞内有机渗透溶质水平会随着细胞内山梨醇或细胞外渗透压的变化而协同反应，以维持细胞内环境。我们推测，糖尿病中葡萄糖诱导的山梨醇蓄积会导致周围神经中牛磺酸耗竭，这可能会损害神经再生，并引发神经元兴奋性增高和疼痛。本研究探讨了大鼠神经中牛磺酸、肌醇和山梨醇之间的关系及其对神经传导速度的影响。测定了非糖尿病大鼠和链脲佐菌素诱导的糖尿病大鼠坐骨神经中的渗透溶质水平和神经传导速度，这些大鼠有的补充了牛磺酸或肌醇，有的未补充。随着山梨醇蓄积，糖尿病神经中的牛磺酸水平下降了31%（p<0.01），肌醇水平下降了37%（p<0.05）。给糖尿病动物补充牛磺酸不影响神经传导速度，但会进一步降低神经肌醇水平。与未治疗的糖尿病动物相比，用醛糖还原酶抑制剂索比尼尔预防山梨醇蓄积可使神经牛磺酸水平提高22%（p<0.05）。因此，我们证明了神经内有机渗透溶质之间的相互依存关系。一种渗透溶质的异常蓄积会导致其他渗透溶质的相互耗竭。糖尿病性神经病变可能是适应性渗透调节不良的一个例子，牛磺酸耗竭会加剧神经损伤和不稳定性。
