Beneficial effects of exendin-4 on experimental polyneuropathy in diabetic mice.
Beneficial effects of exendin-4 on experimental polyneuropathy in diabetic mice.
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DOI：
10.2337/db10-1462
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发表时间：
2011-09
期刊：
影响因子：
7.7
通讯作者：
Nakamura J
中科院分区：
文献类型：
--
作者：
Himeno T;Kamiya H;Naruse K;Harada N;Ozaki N;Seino Y;Shibata T;Kondo M;Kato J;Okawa T;Fukami A;Hamada Y;Inagaki N;Seino Y;Drucker DJ;Oiso Y;Nakamura J
研究了胰高血糖素样肽-1受体（GLP-1 R）激动剂exendin-4对链脲佐菌素（STZ）诱导的糖尿病小鼠糖尿病多发性神经病（DPN）的治疗潜力。通过免疫组织化学分析评价GLP-1 R在腰背根神经节（DRG）中的存在。从C57 BL 6/J小鼠解剖DRG神经元，并在存在或不存在GLP-1（7-37）或毒蜥外泌肽-4的情况下，用或不用施万细胞条件培养基培养。然后测定神经突生长。在动物模型实验中，通过STZ给药使小鼠患糖尿病，糖尿病12周后，每天一次腹腔内给药exendin-4（10 nmol/kg），持续4周。外周神经功能测定采用电流感觉阈值、运动神经传导速度（MNCV）和感觉神经传导速度（SNCV）。坐骨神经血流量（SNBF）和表皮内神经纤维密度（IENFDs）也进行了评价。证实了GLP-1 R在DRG神经元中的表达。GLP-1（7-37）和exendin-4显著促进DRG神经元的突起生长。两种GLP-1 R激动剂均加速了用模拟糖尿病状况的许旺细胞条件培养基培养的DRG神经元受损的轴突生长。在使用的剂量下，exendin-4对血糖或HbA 1c水平没有影响。Exendin-4可改善糖尿病小鼠的痛觉减退和延迟MNCV和SNCV，而不影响SNBF的降低。Exendin-4可改善糖尿病小鼠足底皮肤IENFDs的减少。我们的研究结果表明，exendin-4改善DPN的严重程度，这可能是通过其对DRG神经元及其轴突的直接作用来实现的。
The therapeutic potential of exendin-4, an agonist of the glucagon-like peptide-1 receptor (GLP-1R), on diabetic polyneuropathy (DPN) in streptozotocin (STZ)-induced diabetic mice was investigated. The presence of the GLP-1R in lumbar dorsal root ganglion (DRG) was evaluated by immunohistochemical analyses. DRG neurons were dissected from C57BL6/J mice and cultured with or without Schwann cell–conditioned media in the presence or absence of GLP-1 (7–37) or exendin-4. Then neurite outgrowth was determined. In animal-model experiments, mice were made diabetic by STZ administration, and after 12 weeks of diabetes, exendin-4 (10 nmol/kg) was intraperitoneally administered once daily for 4 weeks. Peripheral nerve function was determined by the current perception threshold and motor and sensory nerve conduction velocity (MNCV and SNCV, respectively). Sciatic nerve blood flow (SNBF) and intraepidermal nerve fiber densities (IENFDs) also were evaluated. The expression of the GLP-1R in DRG neurons was confirmed. GLP-1 (7–37) and exendin-4 significantly promoted neurite outgrowth of DRG neurons. Both GLP-1R agonists accelerated the impaired neurite outgrowth of DRG neurons cultured with Schwann cell–conditioned media that mimicked the diabetic condition. At the doses used, exendin-4 had no effect on blood glucose or HbA1c levels. Hypoalgesia and delayed MNCV and SNCV in diabetic mice were improved by exendin-4 without affecting the reduced SNBF. The decreased IENFDs in sole skins of diabetic mice were ameliorated by exendin-4. Our findings indicate that exendin-4 ameliorates the severity of DPN, which may be achieved by its direct actions on DRG neurons and their axons.
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影响因子：
158.5
作者：
GUTNIAK, M;ORSKOV, C;EFENDIC, S
通讯作者：
EFENDIC, S
影响因子：
7.7
作者：
Arakawa M;Mita T;Azuma K;Ebato C;Goto H;Nomiyama T;Fujitani Y;Hirose T;Kawamori R;Watada H
通讯作者：
Watada H
影响因子：
7.7
作者：
Cabou, Cendrine;Campistron, Gerard;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
3.3
作者：
Kimura, R.;Okouchi, M.;Joh, T.
通讯作者：
Joh, T.
影响因子：
7.2
作者：
Burcelin, R.;Knauf, C.;Cani, P. D.
通讯作者：
Cani, P. D.