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Impaired insulin secretion in pancreatic β-cells lacking the sphingosine-1-phosphate_1 receptor

缺乏鞘氨醇-1-磷酸_1 受体的胰腺 β 细胞的胰岛素分泌受损

基本信息

批准号：
18590200
负责人：
SUGA Sechiko
金额：
$ 2.44万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590200/
关键词：
Islet: β-cells S1P_1 receptor Insulin secretion Gi-protein CAMP ERK インスリン分泌 Gi

项目摘要

Pancreatic islet beta cells secrete insulin in response to glucouse stimulation. To elucidate how S1P_1 is involved in such insulin secretion, whole process from insulin generation to its secretion through S1P_1 on pancreatic beta cell was investigated. First, Morphological study of pancreatic islet and islet hormones contents of S1P_1 knocked out mouse (S1P_1KO) were measured compared to Control litter mate.Results 1. Morphological analysis of S1P_1KO showed no clear difference compared to Control. Immunohistochemistry using antibody for Insulin, Glukagon, Somatostatin and IPAA showed similar staining pattern in both groups. 2. Beta cell organelle showed similar morphology using electronic microscopy in both groups. Also, the number of docking beta cell granules to the plasma membrane reached no statistic difference. 3. S1P_1 phosphorylates ERK kinase in response to its ligand, sphingosin-1-phosphate (S1P). Western brotting analysis using phosph-ERK anti-body by S1P stimulatin revealed weaker phosphrylation of ERK in S1P_1KO islet than in Control. 4. S1P_1 receptor belongs to the family of G protein coupled receptor and couples Gi protein exclusively. S1P_1KO islet showed higher cAMP production in response to GLP-1 stimulation than Control islet cAMP specific ELISA.Conclusions 1. S1P_1 had no apparent effect for islet mass and ratio of islet cell composition. 2. S1P_1 in pancreatic beta cell coupled Gi protein.

胰岛β细胞对葡萄糖刺激作出反应而分泌胰岛素。为了阐明S1P_1是如何参与这种胰岛素分泌的，我们研究了胰岛β细胞上从胰岛素产生到通过S1P_1分泌胰岛素的整个过程。首先，对S1P_1基因敲除小鼠（S1P_1KO）的胰岛形态学和胰岛激素含量进行了测定，并与同窝对照小鼠进行了比较。S1P_1KO的形态学分析显示与对照相比没有明显差异。免疫组化显示两组中胰岛素、胰高血糖素、生长抑素和IPAA的染色模式相似。2.两组的β细胞器在电子显微镜下显示出相似的形态。此外，与质膜对接的β细胞颗粒的数量没有达到统计学差异。3. S1P_1磷酸化ERK激酶以响应其配体鞘氨醇-1-磷酸（S1 P）。用磷酸化ERK抗体经S1 P刺激后进行Western印迹分析，结果显示S1P_1KO胰岛细胞ERK磷酸化程度较对照组弱。4. S1P_1受体属于G蛋白偶联受体家族，仅与G i蛋白偶联。S1P_1KO胰岛对GLP-1刺激的cAMP产生量高于对照胰岛cAMP特异性ELISA。S1P_1对胰岛质量和胰岛细胞组成比例无明显影响。2.胰腺β细胞中的S1P_1偶联Gi蛋白。