Berti-Mattera L N, Peterson R G, Eichberg J
J Neurochem. 1986 Dec;47(6):1932-5. doi: 10.1111/j.1471-4159.1986.tb13110.x.
The ability of insulin treatment to reverse altered phosphoinositide metabolism in sciatic nerve from streptozotocin diabetic rats was studied. Diabetes was induced in rats by means of a single injection of streptozotocin. Enhanced incorporation of 32P into phosphatidylinositol-4,5-bisphosphate (PIP2) was detectable as early as 8 days following intravenous injection of streptozotocin and was maximal after 4 weeks. Hormone treatment was initiated at this time by daily injections of protamine zinc insulin followed by the implantation of long-acting insulin osmotic minipumps, and 4 weeks later sciatic nerves were removed and incubated in the presence of [32P]orthophosphate. The increased labeling of PIP2 was completely reversed by hormone administration. In contrast, insulin (0.1 and 1.0 mU/ml) added to the incubation medium failed to reverse the altered pattern of 32P incorporation into PIP2. The uptake of 32P into PIP2 was greater than 80% higher into the proximal than into the distal portion of normal sciatic nerve when these were incubated separately. This metabolic difference was abolished in diabetic rats, although the incorporation into both segments was still significantly higher than in controls. These results strengthen the association of altered nerve PIP2 metabolism with the diabetic state and are consistent with the concept that experimental diabetic neuropathy is a distal axonopathy.
研究了胰岛素治疗逆转链脲佐菌素诱导的糖尿病大鼠坐骨神经中磷酸肌醇代谢改变的能力。通过单次注射链脲佐菌素诱导大鼠患糖尿病。早在静脉注射链脲佐菌素后8天即可检测到32P掺入磷脂酰肌醇-4,5-二磷酸（PIP2）增加，4周后达到最大值。此时开始激素治疗，每天注射精蛋白锌胰岛素，随后植入长效胰岛素渗透微型泵，4周后取出坐骨神经并在[32P]正磷酸盐存在下孵育。激素给药可完全逆转PIP2标记增加的情况。相比之下，添加到孵育培养基中的胰岛素（0.1和1.0 mU/ml）未能逆转32P掺入PIP2的改变模式。当正常坐骨神经的近端和远端分别孵育时，PIP2中32P的摄取近端比远端高80%以上。糖尿病大鼠中这种代谢差异消失，尽管两个节段中的掺入量仍显著高于对照组。这些结果加强了神经PIP2代谢改变与糖尿病状态的关联，并与实验性糖尿病神经病变是一种远端轴突病的概念一致。
