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Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2
Amyloid-β (Aβ), a natural product of cell metabolism, plays a key role in the pathogenesis of Alzheimer’s disease (AD). Epidemiological studies indicate patients with AD have an increased risk of developing type 2 diabetes mellitus (T2DM). Aβ can induce insulin resistance in cultured hepatocytes by...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609589/ https://www.ncbi.nlm.nih.gov/pubmed/23223021 http://dx.doi.org/10.2337/db12-0670 |
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author | Zhang, Yi Zhou, Ben Deng, Bo Zhang, Fang Wu, Jingxia Wang, Yuangao Le, Yingying Zhai, Qiwei |
author_facet | Zhang, Yi Zhou, Ben Deng, Bo Zhang, Fang Wu, Jingxia Wang, Yuangao Le, Yingying Zhai, Qiwei |
author_sort | Zhang, Yi |
collection | PubMed |
description | Amyloid-β (Aβ), a natural product of cell metabolism, plays a key role in the pathogenesis of Alzheimer’s disease (AD). Epidemiological studies indicate patients with AD have an increased risk of developing type 2 diabetes mellitus (T2DM). Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance. However, whether Aβ induces hepatic insulin resistance in vivo is still unclear. Here we show C57BL/6J mice intraperitoneally injected with Aβ42 exhibit increased fasting blood glucose level, impaired insulin tolerance, and hepatic insulin signaling. Moreover, the APPswe/PSEN1dE9 AD model mice intraperitoneally injected with anti-Aβ neutralizing antibodies show decreased fasting blood glucose level and improved insulin sensitivity. Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling. Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice. Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM. |
format | Online Article Text |
id | pubmed-3609589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-36095892014-04-01 Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2 Zhang, Yi Zhou, Ben Deng, Bo Zhang, Fang Wu, Jingxia Wang, Yuangao Le, Yingying Zhai, Qiwei Diabetes Original Research Amyloid-β (Aβ), a natural product of cell metabolism, plays a key role in the pathogenesis of Alzheimer’s disease (AD). Epidemiological studies indicate patients with AD have an increased risk of developing type 2 diabetes mellitus (T2DM). Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance. However, whether Aβ induces hepatic insulin resistance in vivo is still unclear. Here we show C57BL/6J mice intraperitoneally injected with Aβ42 exhibit increased fasting blood glucose level, impaired insulin tolerance, and hepatic insulin signaling. Moreover, the APPswe/PSEN1dE9 AD model mice intraperitoneally injected with anti-Aβ neutralizing antibodies show decreased fasting blood glucose level and improved insulin sensitivity. Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling. Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice. Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM. American Diabetes Association 2013-04 2013-03-14 /pmc/articles/PMC3609589/ /pubmed/23223021 http://dx.doi.org/10.2337/db12-0670 Text en © 2013 by the American Diabetes Association. Readers 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Zhang, Yi Zhou, Ben Deng, Bo Zhang, Fang Wu, Jingxia Wang, Yuangao Le, Yingying Zhai, Qiwei Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2 |
title | Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2 |
title_full | Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2 |
title_fullStr | Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2 |
title_full_unstemmed | Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2 |
title_short | Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2 |
title_sort | amyloid-β induces hepatic insulin resistance in vivo via jak2 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609589/ https://www.ncbi.nlm.nih.gov/pubmed/23223021 http://dx.doi.org/10.2337/db12-0670 |
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