Greene D A, Chakrabarti S, Lattimer S A, Sima A A
J Clin Invest. 1987 May;79(5):1479-85. doi: 10.1172/JCI112977.
Axo-glial dysjunction refers to the disruption of important junctional complexes that anchor terminal loops of myelin to the paranodal axolemma in diabetic human and animal peripheral nerve. Neither axo-glial dysjunction nor the preceeding acute localized paranodal swelling has been specifically attributed to discrete metabolic consequences of insulin deficiency or hyperglycemia. Two metabolic sequelae of hyperglycemia in diabetic nerve, sorbitol accumulation via aldose reductase, and (Na,K)-ATPase deficiency related to myo-inositol depletion, were explored as possible underlying causes of acute paranodal swelling in the spontaneously diabetic bio-breeding rat. 3 wk of insulin replacement, or therapy with an aldose reductase inhibitor or myo-inositol completely reversed paranodal swelling in sural nerve fibers after 3 wk of untreated insulin deficiency. These observations suggest that insulin deficiency and hyperglycemia cause reversible paranodal swelling, and ultimately poorly reversible axo-glial dysjunction, via the myo-inositol-related (Na,K)-ATPase defect rather than by the osmotic effects of sorbitol accumulation within nerve fibers.
轴突-神经胶质分离是指在糖尿病患者和动物的外周神经中，将髓鞘终末环锚定到结旁轴膜的重要连接复合体遭到破坏。轴突-神经胶质分离以及之前出现的急性局限性结旁肿胀，均未明确归因于胰岛素缺乏或高血糖的特定代谢后果。研究了糖尿病神经中高血糖的两个代谢后遗症，即通过醛糖还原酶导致山梨醇积累，以及与肌醇耗竭相关的（钠，钾）-ATP酶缺乏，将其作为自发性糖尿病生物繁殖大鼠急性结旁肿胀的可能潜在原因。在未经治疗的胰岛素缺乏3周后，进行3周的胰岛素替代治疗，或用醛糖还原酶抑制剂或肌醇治疗，可完全逆转腓肠神经纤维的结旁肿胀。这些观察结果表明，胰岛素缺乏和高血糖通过与肌醇相关的（钠，钾）-ATP酶缺陷，而非神经纤维内山梨醇积累的渗透作用，导致可逆的结旁肿胀，并最终导致难以逆转的轴突-神经胶质分离。
