Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose.
Insulin-like growth factor-I prevents apoptosis in sympathetic neurons exposed to high glucose.
复制标题
DOI：
10.1055/s-2007-978704
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
J. Russell;Eva L. Feldman
中科院分区：
文献类型：
--
作者：
J. Russell;Eva L. Feldman
糖尿病自主神经病变是发病率和死亡率的主要原因。然而，其病因和治疗仍不清楚。采用离体大鼠上级颈上神经节糖尿病神经病变模型，研究了IGF-I对高糖环境下神经突起生长和神经元凋亡的保护作用。在葡萄糖水平升高的情况下，类似于在控制不佳的糖尿病患者中观察到的葡萄糖水平（高于对照20 mM），存在神经突生长抑制、神经突口径减小、神经突成珠和神经突生长锥回缩。高糖还诱导神经节神经元凋亡。相反，IGF-I阻止葡萄糖诱导的细胞凋亡和神经突的变化，即使在96小时后。IGF-I受体在对照组和IGF-I治疗组的神经元中均匀分布在整个发育中的神经突和生长锥中，但在单独的高糖条件下并非如此。这些结果表明，高糖抑制神经突起的生长，并启动培养的交感神经元的凋亡，IGF-I改善这些变化。总的来说，这些观察结果表明，糖尿病自主神经病变的许多功能，可以重现在组织培养模型中使用定义的条件，并可能有重要的意义，在定义糖尿病神经病变的病因和治疗。
Diabetic autonomic neuropathy is a major cause of morbidity and mortality. However, its etiology and treatment remain obscure. Using the in vitro rat superior cervical ganglion model of diabetic neuropathy, we studied the neuroprotective effects of IGF-I on neurite growth and neuronal apoptosis in a high-glucose milieu. In the presence of elevated levels of glucose similar to those seen in poorly controlled diabetics (20 mM above control), there is inhibition of neurite growth, reduction in neurite caliber, beading of neurites, and retraction of the neurite growth cone. High glucose also induces apoptosis in ganglion neurons. In contrast, IGF-I prevented both glucose induced apoptosis and changes in neurites, even after 96 hours. The IGF-I receptor was uniformly distributed throughout the developing neurite and growth cone in control and IGF-I treated neurons, but not with high glucose alone. These findings suggest that high glucose inhibits neurite growth and initiates apoptosis in cultured sympathetic primary neurons, and IGF-I ameliorates these changes. Collectively, these observations suggest that many of the features of diabetic autonomic neuropathy can be reproduced in a tissue culture model using defined conditions, and may have important implications in defining the etiology and treatment of diabetic neuropathy.