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学科主题: 生命有机化学
题名: Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion
其他题名: 促葡萄糖依赖胰岛素分泌的新型PKCs小分子活化剂的发现
作者: HAN SHUAI ; Pan HL(潘鹤龄) ; ZHANG JIANHUA ; Tan L(谭立) ; Ma DW(马大为) ; Yuan JY(袁钧瑛) ; Wu JR(吴家睿)
通讯作者: HAN SHUAI ; 潘鹤龄
刊名: Cell Res.
发表日期: 2011
卷: 21, 期:4, 页:588-599
收录类别: SCI
部门归属: 中科院上海生命科学研究院生物化学与细胞生物学研究所; 中科院上海有机化学研究所; 哈佛大学医学院
英文摘要: Using an image-based screen for small molecules that can affect Golgi morphology, we identify a small molecule, Sioc145, which can enlarge the Golgi compartments and promote protein secretion. More importantly, Sioc145 potentiates insulin secretion in a glucose-dependent manner. We show that Sioc145 selectively activates novel protein kinase Cs (nPKCs; delta and epsilon) but not conventional PKCs (cPKCs; alpha, beta I and beta II) in INS-1E insulinoma cells. In contrast, PMA, a non-selective activator of cPKCs and nPKCs, promotes insulin secretion independent of glucose concentrations. Furthermore, we demonstrate that Sioc145 and PMA show differential abilities in depolarizing the cell membrane, and suggest that Sioc145 promotes insulin secretion in the amplifying pathway downstream of K(ATP) channels. In pancreatic islets, the treatment with Sioc145 enhances the second phase of insulin secretion. Increased insulin granules close to the plasma membrane are observed after Sioc145 treatment. Finally, the administration of Sioc145 to diabetic GK rats increases their serum insulin levels and improves glucose tolerance. Collectively, our studies identify Sioc145 as a novel glucose-dependent insulinotropic compound via selectively activating nPKCs.
语种: 英语
相关网址: 查看原文
WOS记录号: WOS:000289230800006
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/15673
Appears in Collections:生命有机化学国家重点实验室_期刊论文

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Recommended Citation:
HAN SHUAI,Pan HL,ZHANG JIANHUA,et al. Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion[J]. Cell Res.,2011,21(4):588-599.
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