Intranasal Insulin Ameliorates Experimental Diabetic Neuropathy (Retracted Article)
Intranasal Insulin Ameliorates Experimental Diabetic Neuropathy (Retracted Article)
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DOI：
10.2337/db08-1287
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发表时间：
2009-04-01
期刊：
影响因子：
7.7
通讯作者：
Toth, Cory
中科院分区：
文献类型：
--
作者：
Francis, George;Martinez, Jose;Toth, Cory
目的：我们假设，与皮下胰岛素（S-I）相比，鼻内胰岛素（I-I）可靶向神经系统治疗实验性链脲佐菌素诱导的糖尿病周围神经病变（DPN），同时避免潜在的全身不良反应。研究设计和方法：在糖尿病和非糖尿病CD1小鼠8个月期间，分别给予每日0.87 IU的i - i或S-I或安慰剂。采用放射标记胰岛素检测比较I-I和S-I的递送和生物分布。两周行为测试和每月电生理和定量研究评估DPN的进展。在终点和终点前，对DRG、周围神经、远端表皮神经支配和特异性分子标记进行形态学分析。结果：放射性标记的I-I - 1能更快速、更集中地递送到脊髓和DRG，同时减少全身胰岛素暴露。与S-I或鼻内安慰剂相比，I-I - i降低了小鼠的总体死亡率和感觉丧失，同时改善了糖尿病小鼠的神经性疼痛和电生理/形态学异常。I-I - i使糖尿病DRGs中磷酸肌苷3-激酶/Akt、环AMP反应元件结合蛋白和糖原合成酶激酶3 β的mRNA和蛋白水平恢复到接近正常水平。结论：与S-I相比，S-I- i减缓了链脲佐菌素小鼠实验性DPN的进展，避免了S-I治疗相关的不良反应，并延长了寿命。我可能是治疗糖尿病周围神经病变的好方法。糖尿病杂志，2009
OBJECTIVE-We hypothesized that intranasal insulin (I-I) delivery targets the nervous system while avoiding potential adverse systemic effects when compared with subcutaneous insulin (S-I) for experimental streptozotocin-induced diabetic peripheral neuropathy (DPN).RESEARCH DESIGN AND METHODS-I-I or S-I at 0.87 IU daily or placebo were delivered in separate cohorts of diabetic and nondiabetic CD1 mice during 8 months of diabetes. Radiolabeled insulin detection was used to compare delivery and biodistribution for I-I and S-I. Biweekly behavioral testing and monthly electrophysiological and quantitative studies assessed progression of DPN. At and before end point, morphometric analysis of DRG, peripheral nerve, distal epidermal innervation, and specific molecular markers were evaluated.RESULTS-Radiolabeled I-I resulted in more rapid and concentrated delivery to the spinal cord and DRG with less systemic insulin exposure. When compared with S-I or intranasal placebo, I-I reduced overall mouse mortality and sensory loss while improving neuropathic pain and electrophysiological/morphological abnormalities in diabetic mice. I-I restored mRNA and protein levels of phosphoinositide 3-kinase/Akt, cyclic AMP response element-binding protein, and glycogen synthase kinase 3 beta to near normal levels within diabetic DRGs.CONCLUSIONS-I-I slows the progression of experimental DPN in streptozotocin mice, avoids adverse effects associated with S-I treatment, and prolongs lifespan when compared with S-I. I-I may be a promising approach for the treatment of DPN. Diabetes 58:934-945, 2009