DIABETIC NEUROPATHY--RECEPTORS AND SIGNALING MECHANISM

本申请旨在鉴定受体介导的信号通路 及其在实验性糖尿病神经病变中作用。 在之前培养的许旺细胞的研究中，她已经证明， 内皮素调节环磷酸腺苷、磷酸肌醇和 离子钙 她现在将描述内皮素的表达 受体，并研究其表达的变化， 实验性糖尿病时ET-1的表达 在大鼠中由链脲佐菌素诱导。 然后她会检查信号 内皮素调节的途径，包括G蛋白的作用， 磷脂酶C、腺苷酸环化酶和钠的活性， 钾ATP酶 最后，她将研究孵化的影响， 永生化雪旺细胞在高葡萄糖培养基上的基础和 内皮素驱动的信号传导和细胞增殖，并检查 通过减少高葡萄糖引起的影响的可逆性 葡萄糖或肌醇补充剂。

This application Aims to identify receptor-mediated signaling pathways in peripheral nerve and their role in experimental diabetic neuropathy. In prior work with cultured Schwann cells, she has shown that endothelins regulate levels of cyclic AMP, inositol phosphates, and ionized calcium. She will now characterize the expression of endothelin receptors in peripheral nerve, and study changes in their expression and affinity, and in the expression of ET-1, during experimental diabetes induced in rats by strepto-zotocin. Then she will examine the signaling pathways modulated by endothelins, including the roles of G proteins, the activities of phospholipase C, adenylyl cyclase, and sodium, potassium ATPase. Finally, she will examine the effects if incubation of immortalized Schwann cells in high glucose media on basal and endothelin-driven signaling and cell proliferation, and examine the reversibility of the effects of high glucose elicited by diminishing glucose or myo-inositol supplements.