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ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes
Type 2 diabetes (T2D) mellitus is a chronic inflammatory disease characterized with high secretion of tumor necrosis factor (TNF)-α, but the regulatory pathway of TNF-α production in T2D has not been fully elucidated. ASK1-interacting protein 1 (AIP1) is a signaling scaffold protein that modulates s...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196954/ https://www.ncbi.nlm.nih.gov/pubmed/35712257 http://dx.doi.org/10.3389/fendo.2022.896753 |
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author | Song, Zhigao Chen, Cong He, Jipei Liu, Bixia Ji, Weidong Wu, Liangping He, Li |
author_facet | Song, Zhigao Chen, Cong He, Jipei Liu, Bixia Ji, Weidong Wu, Liangping He, Li |
author_sort | Song, Zhigao |
collection | PubMed |
description | Type 2 diabetes (T2D) mellitus is a chronic inflammatory disease characterized with high secretion of tumor necrosis factor (TNF)-α, but the regulatory pathway of TNF-α production in T2D has not been fully elucidated. ASK1-interacting protein 1 (AIP1) is a signaling scaffold protein that modulates several pathways associated with inflammation. In this study, we aimed to investigate the role of AIP1 in T2D development. Our results revealed that AIP1 was downregulated in omental adipose tissue (OAT) of obese patients with T2D compared with that in obese patients. In addition, Pearson’s correlation test showed that AIP1 was negatively correlated with the homeostatic model assessment for insulin resistance (HOMA-IR, r = -0.4829) and waist-to-hip ratio (r = -0.2614), which are major clinical indexes of T2D. As revealed by the proteomic analysis, immunohistochemistry, and ELISA, the OAT and the serum of obese patients with T2D presented high inflammatory status. And the increased inflammatory factors TNF-α and C-reactive protein C (CRP) in the serum of obese patients with T2D showed a positive correlation with HOMA-IR (TNF-α, r = 0.4728; CRP, r = 0.5522). Interestingly, AIP1 deficiency in adipocytes facilitated TNF-α secretion and retarded glucose uptake. Mechanistically, AIP1 deletion in human adipocytes activated JNK, p38 MAPK, and ERK1/2 signaling. Furthermore, inhibition of these signaling pathways using specific inhibitors could suppress these signal activation and insulin resistance caused by AIP1 deficiency. In addition, AIP1 and TNF-α expression in the OAT of patients with T2D recovered to normal levels after laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. These findings indicate that AIP1 is negatively correlated with the clinical indexes of T2D. It modulates TNF-α expression in OAT via JNK, p38 MAPK, and ERK1/2 signaling. |
format | Online Article Text |
id | pubmed-9196954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91969542022-06-15 ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes Song, Zhigao Chen, Cong He, Jipei Liu, Bixia Ji, Weidong Wu, Liangping He, Li Front Endocrinol (Lausanne) Endocrinology Type 2 diabetes (T2D) mellitus is a chronic inflammatory disease characterized with high secretion of tumor necrosis factor (TNF)-α, but the regulatory pathway of TNF-α production in T2D has not been fully elucidated. ASK1-interacting protein 1 (AIP1) is a signaling scaffold protein that modulates several pathways associated with inflammation. In this study, we aimed to investigate the role of AIP1 in T2D development. Our results revealed that AIP1 was downregulated in omental adipose tissue (OAT) of obese patients with T2D compared with that in obese patients. In addition, Pearson’s correlation test showed that AIP1 was negatively correlated with the homeostatic model assessment for insulin resistance (HOMA-IR, r = -0.4829) and waist-to-hip ratio (r = -0.2614), which are major clinical indexes of T2D. As revealed by the proteomic analysis, immunohistochemistry, and ELISA, the OAT and the serum of obese patients with T2D presented high inflammatory status. And the increased inflammatory factors TNF-α and C-reactive protein C (CRP) in the serum of obese patients with T2D showed a positive correlation with HOMA-IR (TNF-α, r = 0.4728; CRP, r = 0.5522). Interestingly, AIP1 deficiency in adipocytes facilitated TNF-α secretion and retarded glucose uptake. Mechanistically, AIP1 deletion in human adipocytes activated JNK, p38 MAPK, and ERK1/2 signaling. Furthermore, inhibition of these signaling pathways using specific inhibitors could suppress these signal activation and insulin resistance caused by AIP1 deficiency. In addition, AIP1 and TNF-α expression in the OAT of patients with T2D recovered to normal levels after laparoscopic Roux-en-Y gastric bypass (RYGB) surgery. These findings indicate that AIP1 is negatively correlated with the clinical indexes of T2D. It modulates TNF-α expression in OAT via JNK, p38 MAPK, and ERK1/2 signaling. Frontiers Media S.A. 2022-05-30 /pmc/articles/PMC9196954/ /pubmed/35712257 http://dx.doi.org/10.3389/fendo.2022.896753 Text en Copyright © 2022 Song, Chen, He, Liu, Ji, Wu and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Song, Zhigao Chen, Cong He, Jipei Liu, Bixia Ji, Weidong Wu, Liangping He, Li ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes |
title | ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes |
title_full | ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes |
title_fullStr | ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes |
title_full_unstemmed | ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes |
title_short | ASK1-Interacting Protein 1 Acts as a Novel Predictor of Type 2 Diabetes |
title_sort | ask1-interacting protein 1 acts as a novel predictor of type 2 diabetes |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196954/ https://www.ncbi.nlm.nih.gov/pubmed/35712257 http://dx.doi.org/10.3389/fendo.2022.896753 |
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