NGBR is required to ameliorate type 2 diabetes in mice by enhancing insulin sensitivity

Chen, Yi; Hu, Wenquan; Li, Qi; Zhao, Shankun; Zhao, Dan; Zhang, Shuang; Zhuo, Wei; Yang, Xiaoxiao; Chen, Yuanli; Li, Xiaoju; Liao, Chenzhong; Han, Jihong; Miao, Qing; Duan, Yajun

doi:10.1016/j.jbc.2021.100624

Cited by 12 publications

(13 citation statements)

References 64 publications

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“…ER stress and inflammation are observed in various pathologic situations. Our lab previously demonstrated that the knockdown of NGBR in HepG2 cells increased ER stress ( Chen et al, 2021 ). PPARγ knockout (PPARγ −/- ) mice are developed spontaneous chronic inflammation in lung ( Malur et al, 2009 ).…”

Section: Resultsmentioning

confidence: 99%

“…Rosiglitazone improves systemic insulin sensitivity by activating AMPK and enhancing skeletal muscle glucose uptake ( Fryer et al, 2002 ). In this regard, we previously determined that liver NGBR specific knockout was associated with insulin resistance and loss of β-cells in pancreas ( Chen et al, 2021 ). Conversely, overexpression of NGBR in the liver improved insulin sensitivity by activating AMPKα and insulin signaling pathways ( Chen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, we previously determined that liver NGBR specific knockout was associated with insulin resistance and loss of β-cells in pancreas ( Chen et al, 2021 ). Conversely, overexpression of NGBR in the liver improved insulin sensitivity by activating AMPKα and insulin signaling pathways ( Chen et al, 2021 ). In the current study, we found PPARγ activation increased NGBR expression, which was related to enhanced AKT phosphorylation ( Figures 2 , 4A ), indicating the PPARγ-enhanced insulin sensitivity may relate to its induction of NGBR expression.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies demonstrate that overexpression of NGBR improves glucosamine hydrochloride (Glcn)-induced ER stress. Likewise, overexpression of NGBR in the liver reduced ER stress and increased insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-treated mice tissues, suggesting that hepatic NGBR may be necessary to maintain insulin sensitivity and prevent type 2 diabetes (T2D) ( Chen et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptor-Gamma Reduces ER Stress and Inflammation via Targeting NGBR Expression

Zeng

Liu

et al. 2022

Front. Pharmacol.

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Increased Nogo-B receptor (NGBR) expression in the liver improves insulin sensitivity by reducing endoplasmic reticulum stress (ER stress) and activating the AMPK pathway, although it remains elusive the mechanisms by which NGBR is induced. In this study, we found that PPARγ ligands (rosiglitazone or pioglitazone) increased NGBR expression in hepatic cells and HUVECs. Furthermore, promoter analysis defined two PPREs (PPARγ-responsive elements) in the promoter region of NGBR, which was further confirmed by the ChIP assay. In vivo, using liver-specific PPARγ deficient (PPARγLKO) mice, we identified the key role of PPARγ expression in pioglitazone-induced NGBR expression. Meanwhile, the basal level of ER stress and inflammation was slightly increased by NGBR knockdown. However, the inhibitory effect of rosiglitazone on inflammation was abolished while rosiglitazone-inhibited ER stress was weakened by NGBR knockdown. Taken together, these findings show that NGBR is a previously unrecognized target of PPARγ activation and plays an essential role in PPARγ-reduced ER stress and inflammation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Peroxisome Proliferator-Activated Receptor-Gamma Reduces ER Stress and Inflammation via Targeting NGBR Expression

Zeng

Liu

et al. 2022

Front. Pharmacol.

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“…S12 ). In addition, our previous article has demonstrated that neither NGBR overexpression nor NGBR inhibition affected Nogo-B expression ( 42 ). These results suggest that Nogo-B and NGBR may exert their functions independently.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of high-fat diet–induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms

Wang

Yang

Zhao

et al. 2022

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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NUS1 Variants Cause Lennox-Gastaut Syndrome Related to Unfolded Protein Reaction Activation

Shen,

Qu,

et al. 2024

Mol Neurobiol

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NGBR is required to ameliorate type 2 diabetes in mice by enhancing insulin sensitivity

Cited by 12 publications

References 64 publications

Peroxisome Proliferator-Activated Receptor-Gamma Reduces ER Stress and Inflammation via Targeting NGBR Expression

Peroxisome Proliferator-Activated Receptor-Gamma Reduces ER Stress and Inflammation via Targeting NGBR Expression

Inhibition of high-fat diet–induced obesity via reduction of ER-resident protein Nogo occurs through multiple mechanisms

NUS1 Variants Cause Lennox-Gastaut Syndrome Related to Unfolded Protein Reaction Activation

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