Inflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)-New Aspects.
Inflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)-New Aspects.
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DOI：
10.3390/ijms221910835
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发表时间：
2021-10-07
影响因子：
5.6
通讯作者：
Nowicki M
中科院分区：
文献类型：
--
作者：
Baum P;Toyka KV;Blüher M;Kosacka J;Nowicki M
糖尿病神经病变的发病机制复杂，目前已提出多种致病途径。为了开发新的治疗策略，需要更好地了解病理生理学。在这里，我们总结了使用 1 型和 2 型糖尿病动物模型进行的实验的最新证据，表明低度神经内炎症是糖尿病神经病变的一个方面。我们的实验数据表明，这些轻度炎症过程可能是与表皮内神经纤维变性相关的糖尿病神经病变的常见终末途径。与早期声称高铁含量的毒性作用的报道相反，我们发现了相反的情况，即营养性铁缺乏会导致轻度炎症和纤维变性，而在正常或高非血红素铁营养中，神经组织中没有或仅发现极其轻微的炎症迹象。肥胖和血脂异常似乎也会引发周围神经的轻度炎症，即使在没有明显的糖尿病的情况下，也与神经病变相关。我们的发现可能是最近观察到的人类感觉运动糖尿病神经病的全身促炎症活性的实验模拟。在 1 型糖尿病大鼠模型中，胰岛素治疗可诱发伴有炎症成分的轻度神经病变，导致 HbA1c 突然降低。这与严重糖尿病患者在治疗导致 HbA1c 快速降低后出现小纤维神经病变的观察结果一致。如果可以通过人体组织和干预研究的数据进一步证实炎症发病机制，那么具有不同作用方式的抗炎化合物可能成为治疗或预防糖尿病神经病变的候选药物。
The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways have been proposed. A better understanding of the pathophysiology is warranted for developing novel therapeutic strategies. Here, we summarize recent evidence from experiments using animal models of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facet of diabetic neuropathy. Our experimental data suggest that these mild inflammatory processes are a likely common terminal pathway in diabetic neuropathy associated with the degeneration of intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-iron content, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammation and fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mild inflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to trigger mild inflammation of peripheral nerves, associated with neuropathy even in the absence of overt diabetes mellitus. Our finding may be the experimental analog of recent observations identifying systemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model of type 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulin treatment causing an abrupt reduction in HbA1c. This is in line with observations in patients with severe diabetes developing a small fiber neuropathy upon treatment-induced rapid HbA1c reduction. If the inflammatory pathogenesis could be further substantiated by data from human tissues and intervention studies, anti-inflammatory compounds with different modes of action may become candidates for the treatment or prevention of diabetic neuropathy.
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影响因子：
7.7
作者：
Duncan, BB;Schmidt, MI;Heiss, G
通讯作者：
Heiss, G
影响因子：
2.8
作者：
Bhati, Pooja;Alam, Rizwan;Hussain, M. Ejaz
通讯作者：
Hussain, M. Ejaz
影响因子：
13.6
作者：
Hanewinckel R;van Oijen M;Ikram MA;van Doorn PA
通讯作者：
van Doorn PA
影响因子：
5.6
作者：
Baum P;Koj S;Klöting N;Blüher M;Classen J;Paeschke S;Gericke M;Toyka KV;Nowicki M;Kosacka J
通讯作者：
Kosacka J
影响因子：
11.2
作者：
Gibbons, Christopher H.;Freeman, Roy
通讯作者：
Freeman, Roy