Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion
文献类型：期刊论文
| 作者 | Han, S; Pan, HL; Zhang, JH; Tan, L; Ma, DW; Yuan, JY; Wu, JR |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2011 |
| 卷号 | 21期号:4页码:588-599 |
| 关键词 | PKC insulin secretion glucose dependency Golgi |
| 通讯作者 | Wu, JR (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol, Shanghai 200031, Peoples R China.,jyuan@hms.harvard.edu ; wujr@sibs.ac.cn |
| 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 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | PROTEIN-KINASE-C ; PANCREATIC BETA-CELLS ; SENSITIVE K+ CHANNELS ; MOUSE B-CELLS ; AMPLIFYING PATHWAYS ; GK RAT ; RESISTANCE ; EPSILON ; ISLETS ; MUSCLE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000289230800006 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/778]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Han, S,Pan, HL,Zhang, JH,et al. Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion[J]. CELL RESEARCH,2011,21(4):588-599. |
| APA | Han, S.,Pan, HL.,Zhang, JH.,Tan, L.,Ma, DW.,...&Wu, JR.(2011).Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion.CELL RESEARCH,21(4),588-599. |
| MLA | Han, S,et al."Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion".CELL RESEARCH 21.4(2011):588-599. |
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