Peripheral nervous system insulin resistance in ob/ob mice.
Peripheral nervous system insulin resistance in ob/ob mice.
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DOI：
10.1186/2051-5960-1-15
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发表时间：
2013-05-10
影响因子：
7.1
通讯作者：
Wright DE
中科院分区：
文献类型：
--
作者：
Grote CW;Groover AL;Ryals JM;Geiger PC;Feldman EL;Wright DE
周围神经系统（PNS）胰岛素信号传导的减少是可能导致感觉神经元功能障碍和糖尿病神经病变的机制。神经元胰岛素抵抗与多种神经系统疾病有关，最近的证据表明，原代培养物中的背根神经节（DRG）神经元显示出改变的胰岛素信号传导，但缺乏体内结果。在这里，进行实验来检验胰岛素抵抗小鼠的三七总皂苷在体内表现出改变的胰岛素信号转导的假设。在这些研究中，非糖尿病对照组和 2 型糖尿病 ob/ob 小鼠接受鞘内注射胰岛素或胰岛素样生长因子 1 (IGF-1) 的攻击，并使用蛋白质印迹分析评估 DRG 和坐骨神经中的下游信号传导。结果表明，ob/ob 小鼠其他“胰岛素敏感”组织（即肌肉、脂肪、肝脏）中记录的胰岛素信号异常也存在于 PNS 中。在非糖尿病小鼠中，通过胰岛素和 IGF-1 刺激，观察到坐骨神经和背根神经节的 Akt 激活显着增加；然而，这种反应在 ob/ob 小鼠的两种组织中均减弱。结果还表明，JNK 激活上调和胰岛素受体表达减少可能是感觉神经元内 PNS 胰岛素抵抗的促成机制。这些发现为越来越多的证据表明胰岛素信号传导的改变发生在三七总皂苷中，并且可能是糖尿病神经病变发病机制的关键因素。
A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy.
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影响因子：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
通讯作者：
Gerton, Brooke
影响因子：
7.7
作者：
Brussee, V;Cunningham, FA;Zochodne, DW
通讯作者：
Zochodne, DW
影响因子：
7.7
作者：
Fernyhough, P;Gallagher, A;Tomlinson, DR
通讯作者：
Tomlinson, DR
DOI：
10.1073/pnas.71.1.84
发表时间：
1974-01-01
影响因子：
11.1
作者：
GAVIN, JR;ROTH, J;BUELL, DN
通讯作者：
BUELL, DN
影响因子：
4.8
作者：
Kim, Bhumsoo;McLean, Lisa L.;Feldman, Eva L.
通讯作者：
Feldman, Eva L.