Treatment-Induced Neuropathy in Diabetes (TIND)-Developing a Disease Model in Type 1 Diabetic Rats.
Treatment-Induced Neuropathy in Diabetes (TIND)-Developing a Disease Model in Type 1 Diabetic Rats.
复制标题
糖尿病治疗诱导的神经病变（TIND）-在1型糖尿病大鼠中建立疾病模型。
DOI：
10.3390/ijms22041571
复制
发表时间：
2021-02-04
影响因子：
5.6
通讯作者：
Kosacka J
中科院分区：
文献类型：
--
作者：
Baum P;Koj S;Klöting N;Blüher M;Classen J;Paeschke S;Gericke M;Toyka KV;Nowicki M;Kosacka J
糖尿病治疗诱发神经病变(TIND)的定义是糖化血红蛋白-A1c(HbA1c)突然下降后8周内发生急性神经病变。其潜在的致病机制仍不完全清楚，到目前为止只有一个小鼠模型被探索。这项研究的目的是进一步探索这一假设，即胰岛素诱导的糖化血红蛋白突然下降可能是发生TIND的主要原因。将BB/OKL(BIONAL BRANCHING/OKL，Ottawa Karlsburg Leipzig)糖尿病大鼠随机分为3组，分别给予皮下渗透型胰岛素泵治疗3个月：1组1单位/d，2组1单位/d，3组1单位/d，后2个月2单位/d。我们连续检测了血糖和HbA1c水平，运动和感觉/混合传入传导速度(mNCV和csNCV)以及周围神经的形态，包括表皮内神经纤维密度和坐骨神经中Iba-1(离子钙结合适配器分子1)阳性巨噬细胞的数量。治疗3个月后，只有糖化血红蛋白迅速下降2%以上的BB/OKL组大鼠坐骨神经mNCV较治疗前下降81%(P<0.0 1)，而治疗3个月后HbA1c和HbA1c下降2%(mNCV为初始值的10 6%，p≤0.0 1)。感觉/混合传入神经传导速度也有类似的趋势：BB/OKL大鼠CSNCV降低，HbA1c和Gt；2%迅速下降(csNCV为初始值的90%)，与轻度下降的大鼠(csNCV为初始值的112%，p≤0.01)相比。此外，与HbA1c和Gt；2%下降组相比，HbA1c和Gt；2%下降组的BB/OKL大鼠巨噬细胞的浸润显著增加约50%(p≤0.01)，降钙素基因相关肽(CGRP)阳性神经纤维减少。我们的结论是，由于大剂量胰岛素治疗导致HbA1c的突然下降，BB/OKL大鼠诱导了一种含有炎症成分的轻度急性神经病变。这种实验诱导的神经病变与人类的TIND有一些共同的特征，可能会在TIND的发病机制和治疗研究中进一步探索。
Treatment-induced neuropathy in diabetes (TIND) is defined by the occurrence of an acute neuropathy within 8 weeks of an abrupt decrease in glycated hemoglobin-A1c (HbA1c). The underlying pathogenic mechanisms are still incompletely understood with only one mouse model being explored to date. The aim of this study was to further explore the hypothesis that an abrupt insulin-induced fall in HbA1c may be the prime causal factor of developing TIND. BB/OKL (bio breeding/OKL, Ottawa Karlsburg Leipzig) diabetic rats were randomized in three groups, receiving insulin treatment by implanted subcutaneous osmotic insulin pumps for 3 months, as follows: Group one received 2 units per day; group two 1 unit per day: and group three 1 unit per day in the first month, followed by 2 units per day in the last two months. We serially examined blood glucose and HbA1c levels, motor- and sensory/mixed afferent conduction velocities (mNCV and csNCV) and peripheral nerve morphology, including intraepidermal nerve fiber density and numbers of Iba-1 (ionized calcium binding adaptor molecule 1) positive macrophages in the sciatic nerve. Only in BB/OKL rats of group three, with a rapid decrease in HbA1c of more than 2%, did we find a significant decrease in mNCV in sciatic nerves (81% of initial values) after three months of treatment as compared to those group three rats with a less marked decrease in HbA1c <2% (mNCV 106% of initial values, p ≤ 0.01). A similar trend was observed for sensory/mixed afferent nerve conduction velocities: csNCV were reduced in BB/OKL rats with a rapid decrease in HbA1c >2% (csNCV 90% of initial values), compared to those rats with a mild decrease <2% (csNCV 112% of initial values, p ≤ 0.01). Moreover, BB/OKL rats of group three with a decrease in HbA1c >2% showed significantly greater infiltration of macrophages by about 50% (p ≤ 0.01) and a decreased amount of calcitonin gene related peptide (CGRP) positive nerve fibers as compared to the animals with a milder decrease in HbA1c. We conclude that a mild acute neuropathy with inflammatory components was induced in BB/OKL rats as a consequence of an abrupt decrease in HbA1c caused by high-dose insulin treatment. This experimentally induced neuropathy shares some features with TIND in humans and may be further explored in studies into the pathogenesis and treatment of TIND.
登录
查看更多内容
DOI：
10.1530/joe-16-0377
发表时间：
2017-04
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Hull RL;Willard JR;Struck MD;Barrow BM;Brar GS;Andrikopoulos S;Zraika S
通讯作者：
Zraika S
影响因子：
11.2
作者：
HEININGER, K;STOLL, G;WEKERLE, H
通讯作者：
WEKERLE, H
影响因子：
12.7
作者：
Mohseni, S;Lillesaar, C;Hildebrand, C
通讯作者：
Hildebrand, C
影响因子：
11.2
作者：
Gibbons, Christopher H.;Freeman, Roy
通讯作者：
Freeman, Roy
影响因子：
158.5
作者：
Gerstein, Hertzel C.;Miller, Michael E.;Friedewald, William T.
通讯作者：
Friedewald, William T.