c-Jun amino terminal kinase 1 deficient mice are protected from streptozotocin-induced islet injury |
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Authors: | Fukuda Kyoichi Tesch Greg H Nikolic-Paterson David J |
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Affiliation: | a Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, 3168 Vic., Australia b Monash University Department of Medicine, Monash Medical Centre, Clayton, 3168 Vic., Australia |
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Abstract: | 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, β-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-α production by infiltrating Jnk1−/− macrophages leading to reduced β-cell apoptosis. In conclusion, JNK1 signaling plays an essential role in macrophage induced β-cell apoptosis and the development of hyperglycemia in MLD-STZ induced pancreatic injury. |
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Keywords: | Apoptosis Beta cell Diabetes Hyperglycemia Islet JNK Macrophage Streptozotocin T-cell TNF-α |
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