RFamide-related peptide-3 promotes alpha TC1 clone 6 cell survival likely via GPR147

RFamide-related peptide-3 promotes alpha TC1 clone 6 cell survival likely via GPR147
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RFamide 相关肽 3 可能通过 GPR147 促进 α TC1 克隆 6 细胞存活

DOI:
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发表时间:
2018-09
期刊:
影响因子:
3
通讯作者:
Qiuhe Ji
Qiuhe Ji
中科院分区:
医学3区
文献类型:
--
作者:
Wencheng Zhang;Li Wang;Qiuhe Ji

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2型糖尿病(T2 DM)与胰岛α细胞质量和存活率密切相关。几种类型的RFamide相关肽(RFRPs)参与调节胰岛细胞的增殖和功能。然而,目前对RFamide相关肽-3(RFRP-3)在胰腺α细胞中的作用的了解还很有限。因此,我们研究了RFRP-3受体G蛋白偶联受体147(GPR147)在小鼠胰岛和αTc1克隆6细胞中的表达,并评价了RFRP-3对α细胞的作用。我们发现GPR147在小鼠胰岛和阿尔法细胞系中表达。此外,RFRP-3可促进阿尔法细胞在高血糖和血清饥饿条件下的存活。机制证据表明,Rfrp-3激活了PI3K/AKT和ERK1/2信号转导通路,而GPR147的拮抗剂1-金刚烷酰-Arg-Phe-NH₂(Rf9)阻断了这一功能。这些fi碱基提示了RFRP3在促进α细胞存活方面的一个新的作用,可能是通过GPR147。
Type 2 diabetes mellitus (T2DM) is closely related to islet alpha cell mass and viability. Several types of RFamide-related peptides (RFRPs) are involved in regulating proliferation and function of islet cells. However, current understanding of the role of RFamide-related peptide-3 (RFRP-3) in pancreatic alpha cells is limited. Therefore, we investigated the expression of the RFRP-3 receptor, G protein-coupled receptor 147 (GPR147), in mouse islets and alpha TC1 clone 6 cells, and evaluated the function of RFRP-3 on alpha cells. We show that GPR147 is expressed in mouse islets and alpha cell lines. In addition, RFRP-3 promotes survival of alpha cells under conditions of hyperglycemia and serum starvation. Mechanistic evidence demonstrates that RFRP-3 activated PI3K/AKT and ERK1/2 signaling cascades and treatment with an antagonist of GPR147, 1-adamantanecarbonyl-Arg-Phe-NH₂ (RF9) blocked this function. These findings indicate a novel effect of RFRP-3 in promoting alpha cell survival, likely via GPR147..
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