FTO 基因沉默抑制胰岛素分泌：GRINCH 细胞的体外研究。

Silencing of the FTO gene inhibits insulin secretion: An in vitro study using GRINCH cells.

机构信息

Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; Lund University Diabetes Center, Malmoe, Lund University, Sweden.

Lund University Diabetes Center, Malmoe, Lund University, Sweden.

出版信息

Mol Cell Endocrinol. 2018 Sep 5;472:10-17. doi: 10.1016/j.mce.2018.06.003. Epub 2018 Jun 8.

DOI:10.1016/j.mce.2018.06.003

PMID:29890211

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6559235/

Abstract

Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA. However, their impact on insulin secretion is still ambiguous. Here in, we investigated the role of FTO and ARL15 using GRINCH (Glucose-Responsive Insulin-secreting C-peptide-modified Human proinsulin) clonal rat β-cells. GRINCH cells have inserted GFP into the human C-peptide insulin gene. Hence, secreted CpepGFP served to monitor insulin secretion. mRNA silencing of FTO in GRINCH cells showed a significant reduction in glucose but not depolarization-stimulated insulin secretion, whereas ARL15 silencing had no effect. A significant down-regulation of insulin mRNA was observed in FTO knockdown cells. Type-2 Diabetic islets revealed a reduced expression of FTO mRNA. In conclusion, our data suggest that fluorescent CpepGFP released from GRINCH cells may serve as a convenient marker for insulin secretion. Silencing of FTO expression, but not ARL15, inhibits insulin secretion by affecting metabolic signaling.

摘要

脂肪量和肥胖相关基因（FTO）和 ADP-核糖基化因子样 15（ARL15）在人胰岛中的表达与 HbA 呈负相关。然而，它们对胰岛素分泌的影响仍然存在争议。在这里，我们使用葡萄糖反应性胰岛素分泌 C 肽修饰的人前胰岛素（GRINCH）克隆大鼠β细胞研究了 FTO 和 ARL15 的作用。GRINCH 细胞将 GFP 插入到人 C 肽胰岛素基因中。因此，分泌的 CpepGFP 用于监测胰岛素分泌。在 GRINCH 细胞中沉默 FTO 的 mRNA 显示葡萄糖刺激但不是去极化刺激的胰岛素分泌显著减少，而 ARL15 沉默则没有影响。在 FTO 敲低细胞中观察到胰岛素 mRNA 的显著下调。2 型糖尿病胰岛显示 FTO mRNA 的表达减少。总之，我们的数据表明，来自 GRINCH 细胞的荧光 CpepGFP 的释放可作为胰岛素分泌的方便标志物。沉默 FTO 的表达，但不是 ARL15，通过影响代谢信号来抑制胰岛素分泌。