The neuronal Ca2+ sensor protein visinin-like protein-1 is expressed in pancreatic islets and regulates insulin secretion
The neuronal Ca2+ sensor protein visinin-like protein-1 is expressed in pancreatic islets and regulates insulin secretion
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DOI：
10.1074/jbc.m512924200
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发表时间：
2006-08-04
影响因子：
4.8
通讯作者：
Wheeler, Michael B.
中科院分区：
文献类型：
--
作者：
Dai, Feihan F.;Zhang, Yi;Wheeler, Michael B.
Visin-like protein-1（VILIP-1）是调节钙依赖性细胞信号转导的神经元钙传感蛋白家族的成员。VILIP-1主要在大脑中表达，通过调节腺苷酸环化酶增加神经细胞中cAMP的形成，但其在其他组织中的功能作用在很大程度上仍然未知。在这项研究中，我们证明了VILIP-1在小鼠胰岛和β细胞中表达。为了深入了解VILIP-1在β细胞中的功能，我们使用了过表达和小干扰RNA敲低策略。在MIN 6 β细胞系或分离的小鼠胰岛中VILIP-1的过表达对基础胰岛素分泌没有影响，但显著增加葡萄糖刺激的胰岛素分泌。cAMP积累在VILIP-1过表达细胞中升高，蛋白激酶A抑制剂H-89减弱葡萄糖刺激的胰岛素分泌增加。通过细胞电容测量检测到，VILIP-1在分离的小鼠β细胞中的过表达增加了cAMP含量，同时增加了cAMP反应元件结合蛋白基因表达并增强了胞吐作用。相反，VILIP-1敲低的小干扰RNA引起cAMP的积累减少，并产生了显着增加前胰岛素原mRNA，基础胰岛素分泌，和总细胞胰岛素含量。这些细胞中前胰岛素原mRNA的增加归因于胰岛素基因转录的增强。总之，我们已经表明VILIP-1在胰腺β细胞中表达并调节胰岛素分泌。增加VILIP-1以cAMP相关的方式增强胰岛素分泌。VILIP-1的下调伴随着cAMP积累减少，但胰岛素基因转录增加。
Visinin-like protein-1 (VILIP-1) is a member of the neuronal Ca2+ sensor protein family that modulates Ca2+-dependent cell signaling events. VILIP-1, which is expressed primarily in the brain, increases cAMP formation in neural cells by modulating adenylyl cyclase, but its functional role in other tissues remains largely unknown. In this study, we demonstrate that VILIP-1 is expressed in murine pancreatic islets and beta-cells. To gain insight into the functions of VILIP-1 in beta-cells, we used both overexpression and small interfering RNA knockdown strategies. Overexpression of VILIP-1 in the MIN6 beta-cell line or isolated mouse islets had no effect on basal insulin secretion but significantly increased glucose-stimulated insulin secretion. cAMP accumulation was elevated in VILIP-1-overexpressing cells, and the protein kinase A inhibitor H-89 attenuated increased glucose-stimulated insulin secretion. Overexpression of VILIP-1 in isolated mouse beta-cells increased cAMP content accompanied by increased cAMP-responsive element-binding protein gene expression and enhanced exocytosis as detected by cell capacitance measurements. Conversely, VILIP-1 knockdown by small interfering RNA caused a reduction in cAMP accumulation and produced a dramatic increase in preproinsulin mRNA, basal insulin secretion, and total cellular insulin content. The increase in preproinsulin mRNA in these cells was attributed to enhanced insulin gene transcription. Taken together, we have shown that VILIP-1 is expressed in pancreatic beta-cells and modulates insulin secretion. Increased VILIP-1 enhanced insulin secretion in a cAMP-associated manner. Downregulation of VILIP-1 was accompanied by decreased cAMP accumulation but increased insulin gene transcription.