ß-cell specific overexpression of suppressor of cytokine signalling-3 does not protect against multiple low dose streptozotocin induced type 1 diabetes in mice
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We investigated the impact of ß-cell specific overexpression of suppressor of cytokine signalling-3 (SOCS-3) on the development of multiple low dose streptozotocin (MLDSTZ) induced Type 1 diabetes and the possible mechanisms involved. MLDSTZ treatment was administered to RIP-SOCS-3 transgenic and wild-type (wt) mice and progression of hyperglycemia monitored. Isolated islets from both strains were exposed to human IL-1ß (25U/ml) or a combination of human IL-1ß (25U/ml) and murine IFN-¿ (1000U/ml) for 24h or 48h and we investigated the expression of IL-1 receptor antagonist (IL-1Ra) mRNA in islet cells and secretion of IL-1Ra into culture medium. MLDSTZ treatment caused gradual hyperglycemia both in the wt mice and in the transgenic mice with the latter tending to be more sensitive. In vitro experiments on wt and transgenic islets did not reveal any differences in sensitivity to damaging effects of STZ. Exposure of wt islets to IL-1ß or IL-1ß+IFN-¿ seemed to lead to a failing IL-1Ra response from SOCS-3 transgenic islets. It could be that an increased expression of a possible protective molecule against ß-cell destruction may lead to a dampered response of another putative protective molecule. This may have counteracted a protective effect against MLDSTZ in SOCS-3 transgenic mice.
|Status||Udgivet - 30 apr. 2011|