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Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice

Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes, but any treatment toward the development of DPN is not yet available. Axon degeneration is an early feature of many peripheral neuropathies, including DPN. Delay of axon degeneration has benefici...

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Autores principales: Cheng, Yalan, Liu, Jun, Luan, Yi, Liu, Zhiyuan, Lai, Hejin, Zhong, Wuling, Yang, Yale, Yu, Huimin, Feng, Ning, Wang, Hui, Huang, Rui, He, Zhishui, Yan, Menghong, Zhang, Fang, Sun, Yan-Gang, Ying, Hao, Guo, Feifan, Zhai, Qiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804630/
https://www.ncbi.nlm.nih.gov/pubmed/31439642
http://dx.doi.org/10.2337/db18-1233
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author Cheng, Yalan
Liu, Jun
Luan, Yi
Liu, Zhiyuan
Lai, Hejin
Zhong, Wuling
Yang, Yale
Yu, Huimin
Feng, Ning
Wang, Hui
Huang, Rui
He, Zhishui
Yan, Menghong
Zhang, Fang
Sun, Yan-Gang
Ying, Hao
Guo, Feifan
Zhai, Qiwei
author_facet Cheng, Yalan
Liu, Jun
Luan, Yi
Liu, Zhiyuan
Lai, Hejin
Zhong, Wuling
Yang, Yale
Yu, Huimin
Feng, Ning
Wang, Hui
Huang, Rui
He, Zhishui
Yan, Menghong
Zhang, Fang
Sun, Yan-Gang
Ying, Hao
Guo, Feifan
Zhai, Qiwei
author_sort Cheng, Yalan
collection PubMed
description Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes, but any treatment toward the development of DPN is not yet available. Axon degeneration is an early feature of many peripheral neuropathies, including DPN. Delay of axon degeneration has beneficial effects on various neurodegenerative diseases, but its effect on DPN is yet to be elucidated. Deficiency of Sarm1 significantly attenuates axon degeneration in several models, but the effect of Sarm1 deficiency on DPN is still unclear. In this study, we show that Sarm1 knockout mice exhibit normal glucose metabolism and pain sensitivity, and deletion of the Sarm1 gene alleviates hypoalgesia in streptozotocin-induced diabetic mice. Moreover, Sarm1 gene deficiency attenuates intraepidermal nerve fiber loss in footpad skin; alleviates axon degeneration, the change of g-ratio in sciatic nerves, and NAD(+) decrease; and relieves axonal outgrowth retardation of dorsal root ganglia from diabetic mice. In addition, Sarm1 gene deficiency markedly diminishes the changes of gene expression profile induced by streptozotocin in the sciatic nerve, especially some abundant genes involved in neurodegenerative diseases. These findings demonstrate that Sarm1 gene deficiency attenuates DPN in mice and suggest that slowing down axon degeneration is a potential promising strategy to combat DPN.
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spelling pubmed-68046302020-11-01 Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice Cheng, Yalan Liu, Jun Luan, Yi Liu, Zhiyuan Lai, Hejin Zhong, Wuling Yang, Yale Yu, Huimin Feng, Ning Wang, Hui Huang, Rui He, Zhishui Yan, Menghong Zhang, Fang Sun, Yan-Gang Ying, Hao Guo, Feifan Zhai, Qiwei Diabetes Complications Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes, but any treatment toward the development of DPN is not yet available. Axon degeneration is an early feature of many peripheral neuropathies, including DPN. Delay of axon degeneration has beneficial effects on various neurodegenerative diseases, but its effect on DPN is yet to be elucidated. Deficiency of Sarm1 significantly attenuates axon degeneration in several models, but the effect of Sarm1 deficiency on DPN is still unclear. In this study, we show that Sarm1 knockout mice exhibit normal glucose metabolism and pain sensitivity, and deletion of the Sarm1 gene alleviates hypoalgesia in streptozotocin-induced diabetic mice. Moreover, Sarm1 gene deficiency attenuates intraepidermal nerve fiber loss in footpad skin; alleviates axon degeneration, the change of g-ratio in sciatic nerves, and NAD(+) decrease; and relieves axonal outgrowth retardation of dorsal root ganglia from diabetic mice. In addition, Sarm1 gene deficiency markedly diminishes the changes of gene expression profile induced by streptozotocin in the sciatic nerve, especially some abundant genes involved in neurodegenerative diseases. These findings demonstrate that Sarm1 gene deficiency attenuates DPN in mice and suggest that slowing down axon degeneration is a potential promising strategy to combat DPN. American Diabetes Association 2019-11 2019-08-22 /pmc/articles/PMC6804630/ /pubmed/31439642 http://dx.doi.org/10.2337/db18-1233 Text en © 2019 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Complications
Cheng, Yalan
Liu, Jun
Luan, Yi
Liu, Zhiyuan
Lai, Hejin
Zhong, Wuling
Yang, Yale
Yu, Huimin
Feng, Ning
Wang, Hui
Huang, Rui
He, Zhishui
Yan, Menghong
Zhang, Fang
Sun, Yan-Gang
Ying, Hao
Guo, Feifan
Zhai, Qiwei
Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
title Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
title_full Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
title_fullStr Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
title_full_unstemmed Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
title_short Sarm1 Gene Deficiency Attenuates Diabetic Peripheral Neuropathy in Mice
title_sort sarm1 gene deficiency attenuates diabetic peripheral neuropathy in mice
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804630/
https://www.ncbi.nlm.nih.gov/pubmed/31439642
http://dx.doi.org/10.2337/db18-1233
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