c-Jun amino terminal kinase 1 deficient mice are protected from streptozotocin-induced islet injury.
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.
Fukuda
Kyoichi
K
Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, 3168 Vic., Australia.
Tesch
Greg H
GH
Nikolic-Paterson
David J
DJ
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin
D013311:Streptozocin; D048055:Mitogen-Activated Protein Kinase 8