Abstract
BackgroundSolute 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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.
Highlights
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
Treatment with 50 nM and 500 nM insulin resulted in significant dosedependent down-regulation of SLC2A1 expression, indicating that insulin is a regulator of SLC2A1 gene expression at a transcriptional level in decidualizing human endometrial stromal cells (hESC)
forkhead box O1 (FOXO1) inhibition downregulates the expression of SLC2A1 mRNA in decidualizing hESC Insulin transcriptionally inactivates FOXO1 in decidualizing hESC thereby affecting the expression of FOXO1 target genes [13]
Summary
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. Solute carrier family 2 member 1 (SLC2A1; previously known as glucose transporter 1) is the most abundant glucose transporter in the endometrial stromal cells [6]. In contrast to solute carrier family 2 member 4 (SLC2A4; previously known as GLUT4) that relocates from intracellular vesicles to the plasma membrane only upon insulin signaling, SLC2A1 is classically a non-insulin-responsive glucose transporter responsible for the constitutive transport of glucose. Insulin has been shown to regulate expression and to some extent cellular location of SLC2A1 in different tissues [7,8,9]
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