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AGK-2对大鼠原代胰岛葡萄糖刺激的胰岛素分泌的影响

Effect of AGK-2 on glucose-stimulated insulin secretion in isolated rat pancreatic islets
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摘要 目的观察Sirt2特异性抑制剂AGK-2对大鼠胰岛葡萄糖刺激的胰岛素分泌的影响,并探讨其可能机制。方法用免疫组化和免疫细胞化学技术观察Sirt2在胰腺组织、单个胰岛β细胞的表达情况:将分离的大鼠胰岛置于24孔培养板培养,分别在2.8和16.7mmoL/L葡萄糖条件下加AGK-2处理1h后.收集上清,检测胰岛素浓度;抽提蛋白,以Western印迹法检测α-tubulin乙酰化水平;用离子成像技术检测单个胰岛B细胞钙离子浓度的变化。结果免疫组化结果显示,在胰腺中Sirt2主要表达在β细胞胞浆中:Sirt2的特异性抑制剂AGK-2对基础胰岛素分泌无显著影响,但使16.7mmol/L葡萄糖刺激的胰岛素分泌降低,呈剂量依赖性,5μmol/LAGK-2能使胰岛素分泌降低75%;离子成像技术结果显示,AGK-2显著抑制高糖引起的钙离子浓度增加。结论Sirt2抑制剂AGK-2可能通过抑制高糖刺激的β细胞钙离子浓度的增加降低胰岛素分泌。 Objective To observe the effect of AGK-2, a specific inhibitor of Sirt2, on insulin secretion of rat islets, and to explore the possible mechanism. Methods The expression of Sift2 in pancreatic tissue and single primary βcell was observed by immunohistochemistry and immunoeytoehemistry. After the isolated rat islets in 24-cell plates were incubated with AGK-2 for 1 h in the presence of 2.8 and 16.7 mmol/L glucose, the culture medium was taken for insulin assay with RIA. Protein was extracted frmn islets for detecting the acetylation of ct-tubulin with Western blot. The change of Ca2+ concentration in single pancreaticβcell was detected by ion imaging technology. Results The immunohistochemistry result showed that Sirt2 was largely expressed in cytoplasm of β cell in the islet of pancreas. Sift2 was mainly located in cytoplasm ofβ cell. AGK-2 inhibited glucose-stimulated insulin secretion in a dose-dependent manner, without effect on basal insulin secretion. At the concentration of 5 μmol/L, AGK-2 decreased insulin secretion by 75%. The ion imaging technology showed that high glucose-stimulated Ca2+ increase was decreased by AGK-2. Conclusion The specific inhibitor of Sift2, AGK-2 inhibited glucose-stimulated insulin secretion by decreasing the concentration of Ca2+in β cells.
出处 《中华内分泌代谢杂志》 CAS CSCD 北大核心 2013年第3期252-256,共5页 Chinese Journal of Endocrinology and Metabolism
基金 国家自然科学基金项目(81070652,81070617,81170720)
关键词 AGK-2 葡萄糖刺激的胰岛素分泌 钙离子 Α-微管蛋白 AGK-2 Glucose-stimulated insulin secretion Calcium ion α-tubulin
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参考文献15

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