Department of Women's and Children's Health, Karolinska Institutet, Karolinska vägen 37A, 171 76, Stockholm, Sweden.
Women's Health Theme, Karolinska University Hospital, Stockholm, Sweden.
Reprod Biol Endocrinol. 2020 Nov 21;18(1):117. doi: 10.1186/s12958-020-00674-0.
Solute carrier family 2 member 1 (SLC2A1; previously known as glucose transporter 1), is the most abundant glucose transporter in human endometrium and is up-regulated during decidualization, whereas high insulin may have a negative impact on this process. The present study aimed to investigate the effect of insulin on the expression of SLC2A1 and glucose uptake in decidualizing human endometrial stromal cells.
We induced in vitro decidualization of endometrial stromal cells obtained from regularly menstruating healthy non-obese women. The cells were treated with increasing concentrations of insulin, and the involvement of the transcription factor forkhead box O1 (FOXO1) was evaluated using a FOXO1 inhibitor. SLC2A1 mRNA levels were measured by Real-Time PCR and protein levels were evaluated by immunocytochemistry. Glucose uptake was estimated by an assay quantifying the cellular uptake of radioactive glucose. One-way ANOVA, Dunnett's multiple comparisons test and paired t-test were used to determine the statistical significance of the results.
We found that insulin dose-dependently decreased SLC2A1 mRNA levels and decreased protein levels of SLC2A1 in decidualizing human endometrial stromal cells. Transcriptional inactivation of FOXO1 seems to explain at least partly the down-regulation of SLC2A1 by insulin. Glucose uptake increased upon decidualization, whereas insulin treatment resulted in a slight inhibition of the glucose uptake, although not significant for all insulin concentrations.
These results indicate an impairment of decidualization by high concentrations of insulin. Future studies will determine the clinical significance of our results for endometrial function and decidualization in women with insulin resistance and hyperinsulinemia.
溶质载体家族 2 成员 1（SLC2A1；以前称为葡萄糖转运蛋白 1）是人类子宫内膜中最丰富的葡萄糖转运蛋白，在蜕膜化过程中上调，而高胰岛素可能对这一过程产生负面影响。本研究旨在探讨胰岛素对蜕膜化人子宫内膜基质细胞中 SLC2A1 表达和葡萄糖摄取的影响。
我们诱导来自定期月经的健康非肥胖女性的子宫内膜基质细胞体外蜕膜化。用递增浓度的胰岛素处理细胞，并使用 FOXO1 抑制剂评估转录因子叉头框 O1（FOXO1）的参与。通过实时 PCR 测量 SLC2A1 mRNA 水平，并通过免疫细胞化学评估蛋白水平。通过定量测定放射性葡萄糖的细胞摄取来估计葡萄糖摄取。使用单因素方差分析、Dunnett 多重比较检验和配对 t 检验来确定结果的统计学意义。
我们发现胰岛素剂量依赖性地下调蜕膜化人子宫内膜基质细胞中 SLC2A1 mRNA 水平和 SLC2A1 蛋白水平。FOXO1 的转录失活似乎至少部分解释了胰岛素对 SLC2A1 的下调。蜕膜化时葡萄糖摄取增加，而胰岛素处理导致葡萄糖摄取略有抑制，但对于所有胰岛素浓度均不显著。
这些结果表明高浓度胰岛素损害了蜕膜化。未来的研究将确定我们的结果对胰岛素抵抗和高胰岛素血症妇女的子宫内膜功能和蜕膜化的临床意义。
