Drynda Robert, Persaud Shanta J, Bowe James E, Jones Peter M
Cell Physiol Biochem. 2018;45(3):1165-1171. doi: 10.1159/000487357. Epub 2018 Feb 8.
BACKGROUND/AIMS: Insulin-secreting islet β-cells adapt to the insulin resistance associated with pregnancy by increasing functional β-cell mass, but the placental signals involved in this process are not well defined. In the current study, we analysed expression of G-protein coupled receptor (GPCR) mRNAs in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to generate an atlas of potential interactions between the placenta and β-cells to inform future functional studies of islet adaptive responses to pregnancy.
Quantative RT-PCR arrays were used to measure mRNA expression levels of: (i) 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice on gestational days 12 and 18; (ii) 126 islet GPCR ligands in mouse placenta at gestational days 12 and 18.
At gestational day 12, a time of rapid expansion of the β-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79 of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts. Approximately half of the quantifiable placental GPCR ligand genes were of unknown function in β-cells. The expression of some islet GPCR and placental ligand mRNAs varied during pregnancy, with altered expression of both GPCR and ligand mRNAs by gestational day 18.
The current study has revealed numerous potential routes for interaction between the placenta and islets, and offers an atlas to inform further functional studies of their roles in adaptive responses to pregnancy, and in the regulation of the β-cell mass.
背景/目的:胰岛素分泌胰岛β细胞通过增加功能性β细胞量来适应与妊娠相关的胰岛素抵抗,但参与这一过程的胎盘信号尚不明确。在本研究中,我们分析了妊娠期间小鼠胰岛中G蛋白偶联受体(GPCR)mRNA的表达以及胎盘中胰岛GPCR配体mRNA的表达,以生成胎盘与β细胞之间潜在相互作用图谱,为未来关于胰岛对妊娠适应性反应的功能研究提供信息。
使用定量RT-PCR阵列测量以下物质的mRNA表达水平:(i)非妊娠小鼠胰岛、妊娠第12天和第18天分离的小鼠胰岛中的342种GPCR;(ii)妊娠第12天和第18天小鼠胎盘中的126种胰岛GPCR配体。
在妊娠第12天,即β细胞量快速增加的时期,可定量检测到189种胰岛GPCR mRNA,同时在胎盘提取物中可检测到126种已知胰岛GPCR配体mRNA中的79种。约一半可定量的胎盘GPCR配体基因在β细胞中的功能未知。一些胰岛GPCR和胎盘配体mRNA的表达在妊娠期间有所变化,到妊娠第18天,GPCR和配体mRNA的表达均发生改变。
本研究揭示了胎盘与胰岛之间众多潜在的相互作用途径,并提供了一个图谱,为进一步研究它们在妊娠适应性反应及β细胞量调节中的作用的功能研究提供信息。