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Amyloid-beta Induces Hepatic Insulin Resistance by Activating JAK2/STAT3/SOCS-1 Signaling Pathway | |
2012 | |
发表期刊 | DIABETES |
ISSN | 0012-1797 |
卷号 | 61期号:6页码:1434-1443 |
发表状态 | 已发表 |
DOI | 10.2337/db11-0499 |
摘要 | Epidemiological studies indicate that patients with Alzheimer's disease (AD) have an increased risk of developing type 2 diabetes mellitus (T2DM), and experimental studies suggest that AD exacerbates T2DM, but the underlying mechanism is still largely unknown. This study aims to investigate whether amyloid-beta (A beta), a key player in AD pathogenesis, contributes to the development of insulin resistance, as well as the underlying mechanism. We find that plasma A beta 40/42 levels are increased in patients with hyperglycemia. APPswe/PSEN1dE9 transgenic AD model mice with increased plasma A beta 40/42 levels show impaired glucose and insulin tolerance and hyperinsulinemia. Furthermore, A beta impairs insulin signaling in mouse liver and cultured hepatocytes. A beta can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor. Knockdown of SOCS-1 alleviates A beta-induced impairment of insulin signaling. Moreover, JAK2/STAT3 is activated by A beta, and inhibition of JAK2/STAT3 signaling attenuates A beta-induced upregulation of SOCS-1 and insulin resistance in hepatocytes. Our results demonstrate that A beta induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM. Diabetes 61:1434-1443, 2012 |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Endocrinology & Metabolism |
WOS类目 | Endocrinology & Metabolism |
WOS记录号 | WOS:000304490100020 |
出版者 | AMER DIABETES ASSOC |
WOS关键词 | TRANSGENIC MOUSE MODEL ; ALZHEIMERS-DISEASE ; A-BETA ; SCAVENGER RECEPTOR ; PLASMA ; OBESITY ; MEMORY ; MECHANISMS ; PEPTIDES ; MICE |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119850 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Zhai, Qiwei |
作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Inst Nutr Sci,Grad Sch, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, Yi,Zhou, Ben,Zhang, Fang,et al. Amyloid-beta Induces Hepatic Insulin Resistance by Activating JAK2/STAT3/SOCS-1 Signaling Pathway[J]. DIABETES,2012,61(6):1434-1443. |
APA | Zhang, Yi.,Zhou, Ben.,Zhang, Fang.,Wu, Jingxia.,Hu, Yanan.,...&Zhai, Qiwei.(2012).Amyloid-beta Induces Hepatic Insulin Resistance by Activating JAK2/STAT3/SOCS-1 Signaling Pathway.DIABETES,61(6),1434-1443. |
MLA | Zhang, Yi,et al."Amyloid-beta Induces Hepatic Insulin Resistance by Activating JAK2/STAT3/SOCS-1 Signaling Pathway".DIABETES 61.6(2012):1434-1443. |
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