Development of new therapy for type 2 diabetes targeting sphingolipid receptor on pancreatic beta cell

开发针对胰腺β细胞鞘脂受体的2型糖尿病新疗法

• 批准号: 21790858
• 负责人: MIZUKAMI Hiroki
• 金额: $ 2.75万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790858/
• 关键词: スフィンゴ脂質; β細胞; 2型糖尿病; G蛋白共益受容体; S1P1; ベータ細胞; 1型糖尿病; G蛋白共役受容体; Gi; β細胞アポトーシス; 膵島移植; β細胞増殖; インスリン分泌

To evaluate the function of sphingolipid signaling in pancreatic β cells, β cell specific S1P1 knocked out mouse was generated using Cre-Lox P system. βS1P1KO showed no apparent phenotype in vivo. Forskolin potentiated insulin secretion was promoted in isolated islet of βS1P1KO compared to control. In whole islet patch clump, forskolin stimulated hyper-oscillation of Ca^<2+> was observed inβS1P1KO islet even under 500nM S1P. In islet transplantation experiment, marginal number of βS1P1KO islets (100) successively lowered glucose level in STZ induced type 1 diabetic model mouse, but not of control islets. Collectively, inhibition of S1P1 signaling in β cells can lead to protection against β cell injury and lead to a new type of β cell therapy in diabetes.

为了评估胰腺β细胞中的真菌信号传导，使用Cre-lox p在整个Islet Patch Plump中产生了β细胞特异性的S1P1。在胰岛实验中，在500nm的S1P下，βS1P1KO胰岛的边缘数量（100）在STZ诱导的1型糖尿病模型小鼠中的葡萄糖水平。

项目成果

八木橋操六膵島移植における膵β細胞S1P1の役割について

八木桥宗六论胰岛β细胞S1P1在胰岛移植中的作用

• 作者: 水上浩哉;春日加奈子
• 通讯作者: 春日加奈子