Verapamil Attenuated Prediabetic Neuropathy in High-Fat Diet-Fed Mice through Inhibiting TXNIP-Mediated Apoptosis and Inflammation
Joint Authors
Guan, Meiping
Zeng, Yanmei
Xu, Lingling
Lin, Xiaopu
Liu, Yingshan
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-01-10
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Diabetic neuropathy (DN) is a common and severe complication of diabetes mellitus.
There is still a lack of an effective treatment to DN because of its complex pathogenesis.
Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of thioredoxin, has been shown to be associated with diabetic retinopathy and nephropathy.
Herein, we aim to investigate the role of TXNIP in prediabetic neuropathy and therapeutic potential of verapamil which has been shown to inhibit TXNIP expression.
The effects of mediating TXNIP on prediabetic neuropathy and its exact mechanism were performed using high-fat diet- (HFD-) induced diabetic mice and palmitate-treated neurons.
Our results showed that TXNIP upregulation is associated with prediabetic neuropathy in HFD-fed mice.
TXNIP knockdown improved DN in HFD-induced prediabetic mice.
Mechanistically, increased TXNIP in dorsal root ganglion is transferred into the cytoplasm and shuttled to the mitochondria.
In cytoplasm, TXNIP binding to TRX1 results in the increased oxidative stress and inflammation.
In mitochondria, TXNIP binding to TRX2 induced mitochondria dysfunction and apoptosis.
TXNIP isolated from TRX2 then shuttles to the cytoplasm and binds to NLRP3, resulting in further increased TXNIP-NLRP3 complex, which induced the release of IL-1β and the development of inflammation.
Thus, apoptosis and inflammation of dorsal root ganglion neuron eventually cause neural dysfunction.
In addition, we also showed that verapamil, a known inhibitor of calcium channels, improved prediabetic neuropathy in the HFD-fed mice by inhibiting the upregulation of TXNIP.
Our finding suggests that TXNIP might be a potential target for the treatment of neuropathy in prediabetic patients with dyslipidemia.
American Psychological Association (APA)
Xu, Lingling& Lin, Xiaopu& Guan, Meiping& Zeng, Yanmei& Liu, Yingshan. 2019. Verapamil Attenuated Prediabetic Neuropathy in High-Fat Diet-Fed Mice through Inhibiting TXNIP-Mediated Apoptosis and Inflammation. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1202412
Modern Language Association (MLA)
Xu, Lingling…[et al.]. Verapamil Attenuated Prediabetic Neuropathy in High-Fat Diet-Fed Mice through Inhibiting TXNIP-Mediated Apoptosis and Inflammation. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1202412
American Medical Association (AMA)
Xu, Lingling& Lin, Xiaopu& Guan, Meiping& Zeng, Yanmei& Liu, Yingshan. Verapamil Attenuated Prediabetic Neuropathy in High-Fat Diet-Fed Mice through Inhibiting TXNIP-Mediated Apoptosis and Inflammation. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1202412
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202412