Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia.
Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia.
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DOI：
10.1016/j.expneurol.2011.05.025
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发表时间：
2011-12
影响因子：
5.3
通讯作者：
Brines, Michael
中科院分区：
文献类型：
--
作者：
Schmidt, Robert E.;Feng, Dongyan;Wang, Qiuling;Green, Karen G.;Snipes, Lisa L.;Yamin, Michael;Brines, Michael
秋田小鼠是糖尿病自主神经病变的强健模型，在β细胞死亡后发展为严重的糖尿病，在3-4周龄时可重复发生，并且在没有治疗的情况下维持糖尿病状态长达11个月。累及椎前交感肠系膜上神经节和腹腔神经节的神经性营养不良和神经病变在糖尿病发病的头两个月内开始发展，并随着时间的推移而进展。我们研究了胰岛素植入导致血糖正常和注射ARA290的作用，ARA290是一种对血糖参数没有影响的小红细胞生成素肽，对已建立的神经营养不良和神经病变的逆转。我们发现，从糖尿病患者2个月开始进行4周胰岛素治疗可使血糖、体重和糖化血红蛋白恢复正常。胰岛素治疗成功地逆转了已建立的神经性营养不良和神经病变到控制水平。糖尿病和胰岛素治疗3个月的秋田小鼠交感神经元数量均无显著变化。从糖尿病患者4个月开始，用ARA290治疗7周，通过血糖、体重或HbA1c水平测量，没有改变糖尿病代谢严重程度。与未经治疗的糖尿病患者或与代表4个月治疗起始点的另一组糖尿病动物相比，ARA290治疗能够减少神经性营养不良55-74%。令人惊讶的是，在这段时间内，ARA290对糖尿病秋田小鼠的神经节神经元数量或持续的神经病变（苍白/变性神经元）没有影响。神经保护epo样肽的发展可能为这种使人衰弱的糖尿病并发症提供一种可能的未来治疗方法；然而，似乎离散的元素可能是不同的糖尿病状态的目标，可能需要选择性治疗。
The Akita mouse is a robust model of diabetic autonomic neuropathy which develops severe diabetes following beta cell death, which occurs reproducibly at 3-4 weeks of age, and maintains the diabetic state without therapy for as long as 11 additional months. Neuritic dystrophy and neuronopathy involving prevertebral sympathetic superior mesenteric and celiac ganglia begin to develop within the first two months of onset of diabetes and are progressive with time. We have examined the effect of insulin implants resulting in normoglycemia and injections of ARA290, a small erythropoietin peptide which has no effect on glycemic parameters, on the reversal of established neuritic dystrophy and neuronopathy. We have found that 4 weeks of insulin therapy beginning at 2 months of diabetes resulted in normalization of blood glucose, body weight and HbA1c. Insulin therapy successfully reversed established neuritic dystrophy and neuronopathy to control levels. Numbers of sympathetic neurons were not significantly changed in either 3 month diabetic or insulin treated Akita mice. Treatment with ARA290 for 7 weeks beginning at 4 months of diabetes did not result in altered metabolic severity of diabetes as measured by blood glucose, body weight or HbA1c levels. ARA290 treatment was able to decrease neuritic dystrophy by 55-74% compared to untreated diabetics or in comparison to a separate group of diabetic animals representing the 4 month treatment onset point. Surprisingly, there was no effect of ARA290 on ganglionic neuron number or ongoing neuronopathy (pale/degenerating neurons) in diabetic Akita mice during this time period. The development of neuroprotective EPO-like peptides may provide a possible future therapy for this debilitating complication of diabetes; however, it appears that discrete elements may be differentially targeted by the diabetic state and may require selective therapy.
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影响因子：
15.9
作者：
CHANG, EB;BERGENSTAL, RM;FIELD, M
通讯作者：
FIELD, M
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11.4
作者：
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BURNSTOCK, G
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158.5
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