Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion

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	Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion
	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)
刊名	Cell Res.
	2011
卷号	21 期号:4 页码:588-599
ISSN号	1001-0602
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
通讯作者	HAN SHUAI ; 潘鹤龄
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.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1038/cr.2010.137
语种	英语
WOS记录号	WOS:000289230800006
公开日期	2013-02-19
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/15673]
专题	上海有机化学研究所_生命有机化学国家重点实验室
推荐引用方式 GB/T 7714	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.
APA	HAN SHUAI.,潘鹤龄.,ZHANG JIANHUA.,谭立.,马大为.,...&吴家睿.(2011).Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion.Cell Res.,21(4),588-599.
MLA	HAN SHUAI,et al."Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion".Cell Res. 21.4(2011):588-599.