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KMID : 0620920100420090628
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Experimental & Molecular Medicine
2010 Volume.42 No. 9 p.628 ~ p.638
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Sulfuretin protects against cytokine-induced β-cell damage and prevents streptozotocin-induced diabetes
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Song Mi-Young
Jeong Gil-Saeng
Kwon Kang-Beom
Ka Sun-O
Jang Hyun-Young
Park Jin-Woo
Kim Youn-Chul
Park Byung-Hyun
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Abstract
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NF-κB activation has been implicated as a key signaling mechanism for pancreatic β-cell damage. Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the NF-κB pathway. Therefore, we isolated sulfuretin from Rhus verniciflua and evaluated if sulfuretin could inhibit cytokine- or streptozotocin-induced β-cell damage. Rat insulinoma RINm5F cells and isolated rat islets were treated with IL-1β and IFN-γ to induce cytotoxicity. Incubation of cells and islets with sulfuretin resulted in a significant reduction of cytokine-induced NF-κB activation and its downstream events, iNOS expression, and nitric oxide production. The cytotoxic effects of cytokines were completely abolished when cells or islets were pretreated with sulfuretin. The protective effect of sulfuretin was further demonstrated by normal insulin secretion of cytokine-treated islets in response to glucose. Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of streptozotocin were completely prevented when mice were pretreated with sulfuretin. The anti-diabetogenic effects of sulfuretin were also mediated by suppression of NF-κB activation. Collectively, these results indicate that sulfuretin may have therapeutic value in preventing β-cell damage.
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KEYWORD
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cytokines, diabetes mellitus, experimental, NF-κB, Rhus verniciflua, streptozotocin, sulfuretin
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