Study of the molecular mechanism of insulin exocytosis by SNARE hypothesis

SNARE假说研究胰岛素胞吐作用的分子机制

• 批准号: 08457057
• 负责人: NAGAMATSU Shinya
• 金额: $ 2.3万
• 依托单位: Kyorin University school of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457057/
• 关键词: Syntaxin; SNARE; Exocytosis; Pancreatic beta cell; SNAP; Diabetes Medllirus; Pancreatic βcell; インスリン分泌; 膵β細胞; NSF; 調節性分泌機構; 構成性分泌機構; 膵β細部

The molecular mechanism of insulin exocytotic process in pancreatic beta cells is still unknown. Recently ; the fundamental components of the machinery for docking/fusion process have been revealed. These components include NSF, SNAP, and SNAP receptors. In the present project, we studied the functional roles of these components in insulin exocytotic process, and further examined the relationship between SNAP receptors and diabetes mellitus. We summarized the points of this research project as follows.1) Syntaxin lA and SNAP-25 were expressed in pancreatic p cells and the biosynthesis was regulated by glucose.2) alpha-SNAP plays a crucial role in glucose-stimulated insulin exocytosis via large dense core vesicles, but not GABA release via synaptic-like microvesicles inpancreatic beta cells.3) alpha-SNAP functions in insulin exocytosis from mature, but not immature insulin secretory granules.4) Expression of t-SNAREs was decreased in diabetic GK rat islets. Restoration of decreased t-SNARE protein to the normal level improved the impaired insulin release in diabetic GK rat islets.

胰岛素在胰岛β细胞中胞吐过程的分子机制尚不清楚。最近，对接/聚变过程的基本组成部分已经被揭示出来。这些组分包括NSF、SNAP和SNAP受体。本课题旨在研究SNAP受体在胰岛素胞吐过程中的作用，并进一步探讨SNAP受体与糖尿病的关系。本课题的主要研究内容如下：1）Syntaxin 1A和SNAP-25在胰腺β细胞中表达，其生物合成受葡萄糖的调控; 2）α-SNAP在葡萄糖刺激的胰岛素分泌中起重要作用，主要通过大的致密核心囊泡，而不是通过突触样微囊泡释放GABA; 3）α-SNAP在胰岛素分泌中起重要作用，4）糖尿病GK大鼠胰岛中t-SNARE表达减少。降低的t-SNARE蛋白恢复到正常水平改善糖尿病GK大鼠胰岛受损的胰岛素释放。

项目成果

Nagamatsu S.et.al.: "Syntaxin,but not SNAP,biosynthesis by rat pancreatic islets." Diabetologia. 40. 1396-1402 (1997)

Nagamatsu S.et.al.：“大鼠胰岛的生物合成是突触蛋白，但不是 SNAP。”

Nagamatsu S., Nakamichi Y., Yamaguchi K., Sawa H., and Akagawa K.: "Overexpressed syntaxin 1A/HPC-1 inhibits insulin secretion via regulated pathway, but does not influence glucose metabolism aud intracellular Ca^<2+> in insulinoma cell line betaTC3 cells

Nagamatsu S.、Nakamichi Y.、Yamaguchi K.、Sawa H. 和 Akakawa K.：“过表达的突触蛋白 1A/HPC-1 通过调节途径抑制胰岛素分泌，但不影响葡萄糖代谢和细胞内 Ca^2 >

S.Nagamatsu,et.al: "α-soluble N-ethylmaleimide-sensitive factor attachment protein is expressed in pancreatic β cells and functions in insulin,but not gamma-aminobutyric acid secretion" J.Biol.Chem.274. 8053-8060 (1999)

S.Nagamatsu 等人：“α-可溶性 N-乙基马来酰亚胺敏感因子附着蛋白在胰腺 β 细胞中表达，并在胰岛素中发挥作用，但不分泌 γ-氨基丁酸”J.Biol.Chem.274。 (1999)

Nagamatsu S.et.al.: "Overexpressed Syntaxin 1A/hpc1 inhibits insulin secretion." Biochem.Biophys.Res.Commun.231. 89-93 (1997)

Nagamatsu S.et.al.：“过度表达的 Syntaxin 1A/hpc1 会抑制胰岛素分泌。”

S.Nagamatsu et al.: "Overexpressed syntaxin 1A/HPC-1 inhibits insulin secretion via regulated pathway, but does not influence glucose metabolism and intracellular Ca2+ in insulinoma cell line βTC3 cells." Biochem. Biophys. Res.Commun.231. 89-93 (1997)

S.Nagamatsu 等人：“过表达的突触蛋白 1A/HPC-1 通过调节途径抑制胰岛素分泌，但不影响胰岛素瘤细胞系 βTC3 细胞中的葡萄糖代谢和细胞内 Ca2+。”Res.Commun.231。 -93 (1997)