Greene D A, Lattimer S A, Sima A A
N Engl J Med. 1987 Mar 5;316(10):599-606. doi: 10.1056/NEJM198703053161007.
During the past decade, our appreciation of the original experiments with myo-inositol supplementation in diabetic rats has greatly expanded. The effects of myo-inositol on nerve conduction are now explained by concepts that were largely unappreciated in 1976, including the fundamental role of phosphoinositide metabolism in cell regulation and the importance of the activity of sodium-potassium-ATPase in nerve conduction. Aldose reductase inhibitors firmly link defects in myo-inositol metabolism to activation of the polyol pathway in diabetes; the resulting "sorbitol-myo-inositol hypothesis" has been extended from its application to the lenses and peripheral nerves to most of the tissues involved with diabetic complications. These biochemical mechanisms provide a new framework within which to explore the complex interactions between hyperglycemia and the vascular, genetic, and environmental variables in the pathogenesis of diabetic complications. It is anticipated that these endeavors will result in the appearance of new classes of therapeutic agents, the first of which--the aldose reductase inhibitors--has emerged from the laboratory and is now undergoing extensive clinical testing. These efforts are very likely to result in the appearance of new treatment methods that may dramatically lighten the burden of chronic complications in patients with diabetes.
在过去十年中，我们对最初在糖尿病大鼠中补充肌醇的实验的认识有了极大的扩展。现在，肌醇对神经传导的影响可以用1976年时基本上未被认识到的一些概念来解释，包括磷酸肌醇代谢在细胞调节中的基本作用以及钠钾ATP酶活性在神经传导中的重要性。醛糖还原酶抑制剂将肌醇代谢缺陷与糖尿病中多元醇途径的激活紧密联系起来；由此产生的“山梨醇 - 肌醇假说”已从其在晶状体和周围神经中的应用扩展到与糖尿病并发症相关的大多数组织。这些生化机制提供了一个新的框架，在这个框架内可以探索高血糖与糖尿病并发症发病机制中的血管、遗传和环境变量之间的复杂相互作用。预计这些研究将催生出新一类的治疗药物，其中第一种——醛糖还原酶抑制剂——已从实验室问世，目前正在进行广泛的临床试验。这些努力很可能会带来新的治疗方法，可能会极大地减轻糖尿病患者慢性并发症的负担。
