論文 - 詳細
| RRC ID | 78037 |
|---|---|
| 著者 | Lee D, Yoon E, Ham SJ, Lee K, Jang H, Woo D, Lee DH, Kim S, Choi S, Chung J. |
| タイトル | Diabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila. |
| ジャーナル | Nat Commun |
| Abstract |
Diabetic sensory neuropathy (DSN) is one of the most common complications of type 2 diabetes (T2D), however the molecular mechanistic association between T2D and DSN remains elusive. Here we identify ubiquitin C-terminal hydrolase L1 (UCHL1), a deubiquitinase highly expressed in neurons, as a key molecule underlying T2D and DSN. Genetic ablation of UCHL1 leads to neuronal insulin resistance and T2D-related symptoms in Drosophila. Furthermore, loss of UCHL1 induces DSN-like phenotypes, including numbness to external noxious stimuli and axonal degeneration of sensory neurons in flies' legs. Conversely, UCHL1 overexpression improves DSN-like defects of T2D model flies. UCHL1 governs insulin signaling by deubiquitinating insulin receptor substrate 1 (IRS1) and antagonizes an E3 ligase of IRS1, Cullin 1 (CUL1). Consistent with these results, genetic and pharmacological suppression of CUL1 activity rescues T2D- and DSN-associated phenotypes. Therefore, our findings suggest a complete set of genetic factors explaining T2D and DSN, together with potential remedies for the diseases. |
| 巻・号 | 15(1) |
| ページ | 468 |
| 公開日 | 2024-1-11 |
| DOI | 10.1038/s41467-024-44747-9 |
| PII | 10.1038/s41467-024-44747-9 |
| PMID | 38212312 |
| PMC | PMC10784524 |
| MeSH | Animals Diabetes Mellitus, Type 2* / genetics Drosophila Insulin Resistance* / genetics Neurons Ubiquitin Thiolesterase / genetics |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | 7037R-1 1877R-1 7788R-1 HMS01553 3938R-2 5072R-3 GL00039 HMS00476 4006R-1 DGRC#108125 DGRC#108184 |