| First Author | Fukuda K | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 366 |
| Issue | 3 | Pages | 710-6 |
| PubMed ID | 18082135 | Mgi Jnum | J:130705 |
| Mgi Id | MGI:3772142 | Doi | 10.1016/j.bbrc.2007.12.007 |
| Citation | Fukuda K, et al. (2008) c-Jun amino terminal kinase 1 deficient mice are protected from streptozotocin-induced islet injury. Biochem Biophys Res Commun 366(3):710-6 |
| abstractText | In vitro studies have implicated the c-Jun amino terminal kinase (JNK) in cytokine-induced pancreatic injury leading to a loss of insulin production and hyperglycemia. We examined the role of JNK1 in the multiple low dose streptozotocin (MLD-STZ) model in which islet injury and hyperglycemia are dependent upon T cell immunity and pro-inflammatory cytokines. MLD-STZ in wild type mice induced islet leukocyte infiltration, cytokine production, beta-cell apoptosis, and hyperglycemia. In contrast, Jnk1-/- mice were substantially protected from a loss of insulin producing cells and hyperglycemia in the MLD-STZ model despite a marked islet T cell and macrophage infiltrate. Based upon several lines of evidence, this protection was attributed to a reduction in TNF-alpha production by infiltrating Jnk1-/- macrophages leading to reduced beta-cell apoptosis. In conclusion, JNK1 signaling plays an essential role in macrophage induced beta-cell apoptosis and the development of hyperglycemia in MLD-STZ induced pancreatic injury. |
