| First Author | Zhang Y | Year | 2012 |
| Journal | Diabetes | Volume | 61 |
| Issue | 6 | Pages | 1434-43 |
| PubMed ID | 22522613 | Mgi Jnum | J:196823 |
| Mgi Id | MGI:5489984 | Doi | 10.2337/db11-0499 |
| Citation | Zhang Y, et al. (2012) Amyloid-beta induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway. Diabetes 61(6):1434-43 |
| abstractText | 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 (Abeta), a key player in AD pathogenesis, contributes to the development of insulin resistance, as well as the underlying mechanism. We find that plasma Abeta40/42 levels are increased in patients with hyperglycemia. APPswe/PSEN1dE9 transgenic AD model mice with increased plasma Abeta40/42 levels show impaired glucose and insulin tolerance and hyperinsulinemia. Furthermore, Abeta impairs insulin signaling in mouse liver and cultured hepatocytes. Abeta can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor. Knockdown of SOCS-1 alleviates Abeta-induced impairment of insulin signaling. Moreover, JAK2/STAT3 is activated by Abeta, and inhibition of JAK2/STAT3 signaling attenuates Abeta-induced upregulation of SOCS-1 and insulin resistance in hepatocytes. Our results demonstrate that Abeta induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM. |
