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Published in: Reproductive Biology and Endocrinology 1/2020

Open Access 01-12-2020 | Insulins | Research

Insulin regulation of solute carrier family 2 member 1 (glucose transporter 1) expression and glucose uptake in decidualizing human endometrial stromal cells: an in vitro study

Authors: Ivika Jakson, Dorina Ujvari, Sebastian Brusell Gidlöf, Angelica Lindén Hirschberg

Published in: Reproductive Biology and Endocrinology | Issue 1/2020

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Abstract

Background

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.

Methods

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.

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.

Conclusions

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.
Literature
1.
go back to reference Zhu H, Hou CC, Luo LF, Hu YJ, Yang WX. Endometrial stromal cells and decidualized stromal cells: origins, transformation and functions. Gene. 2014;551(1):1-14. Zhu H, Hou CC, Luo LF, Hu YJ, Yang WX. Endometrial stromal cells and decidualized stromal cells: origins, transformation and functions. Gene. 2014;551(1):1-14.
2.
go back to reference Pan-Castillo B, Gazze SA, Thomas S, Lucas C, Margarit L, Gonzalez D, et al. Morphophysical dynamics of human endometrial cells during decidualization. Nanomed Nanotechnol Biol Med. 2018;14(7):2235-45. Pan-Castillo B, Gazze SA, Thomas S, Lucas C, Margarit L, Gonzalez D, et al. Morphophysical dynamics of human endometrial cells during decidualization. Nanomed Nanotechnol Biol Med. 2018;14(7):2235-45.
3.
go back to reference Salker M, Teklenburg G, Molokhia M, Lavery S, Trew G, Aojanepong T, et al. Natural selection of human embryos: impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss. PLoS One. 2010;5(4):e10287. Salker M, Teklenburg G, Molokhia M, Lavery S, Trew G, Aojanepong T, et al. Natural selection of human embryos: impaired decidualization of endometrium disables embryo-maternal interactions and causes recurrent pregnancy loss. PLoS One. 2010;5(4):e10287.
4.
go back to reference Conrad KP, Rabaglino MB, Post Uiterweer ED. Emerging role for dysregulated decidualization in the genesis of preeclampsia. Placenta. 2017;60:119-29. Conrad KP, Rabaglino MB, Post Uiterweer ED. Emerging role for dysregulated decidualization in the genesis of preeclampsia. Placenta. 2017;60:119-29.
5.
go back to reference Dean M. Glycogen in the uterus and fallopian tubes is an important source of glucose during early pregnancy†. Biol Reprod. 2019;101(2):297-305. Dean M. Glycogen in the uterus and fallopian tubes is an important source of glucose during early pregnancy†. Biol Reprod. 2019;101(2):297-305.
6.
go back to reference Frolova AI, Moley KH. Glucose transporters in the uterus: an analysis of tissue distribution and proposed physiological roles. Reproduction. 2011;142(2):211–20.CrossRef Frolova AI, Moley KH. Glucose transporters in the uterus: an analysis of tissue distribution and proposed physiological roles. Reproduction. 2011;142(2):211–20.CrossRef
7.
go back to reference Devaskar SU, Mueckler MM. The mammalian glucose transporters. Pediatr Res. 1992;31:1-13. Devaskar SU, Mueckler MM. The mammalian glucose transporters. Pediatr Res. 1992;31:1-13.
8.
go back to reference Taha C, Mitsumoto Y, Liu Z, Skolnik EY, Klip A. The insulin-dependent biosynthesis of GLUT1 and GLUT3 glucose transporters in L6 muscle cells is mediated by distinct pathways. Roles of p21(ras) and pp70 S6 kinase. J Biol Chem. 1995;270(42):24678-81. Taha C, Mitsumoto Y, Liu Z, Skolnik EY, Klip A. The insulin-dependent biosynthesis of GLUT1 and GLUT3 glucose transporters in L6 muscle cells is mediated by distinct pathways. Roles of p21(ras) and pp70 S6 kinase. J Biol Chem. 1995;270(42):24678-81.
9.
go back to reference Taha C, Liu Z, Jin J, Al-Hasani H, Sonenberg N, Klip A. Opposite translational control of GLUT1 and GLUT4 glucose transporter mRNAs in response insulin. Role of mammalian target of rapamycin, protein kinase B, and phosphatidylinositol 3-kinase in GLUT1 mRNA translation. J Biol Chem. 1999;274(46):33085-91. Taha C, Liu Z, Jin J, Al-Hasani H, Sonenberg N, Klip A. Opposite translational control of GLUT1 and GLUT4 glucose transporter mRNAs in response insulin. Role of mammalian target of rapamycin, protein kinase B, and phosphatidylinositol 3-kinase in GLUT1 mRNA translation. J Biol Chem. 1999;274(46):33085-91.
10.
go back to reference Frolova A, Flessner L, Chi M, Kim ST, Foyouzi-Yousefi N, Moley KH. Facilitative glucose transporter type 1 is differentially regulated by progesterone and estrogen in murine and human endometrial stromal cells. Endocrinology. 2009;150(3):1512–20.CrossRef Frolova A, Flessner L, Chi M, Kim ST, Foyouzi-Yousefi N, Moley KH. Facilitative glucose transporter type 1 is differentially regulated by progesterone and estrogen in murine and human endometrial stromal cells. Endocrinology. 2009;150(3):1512–20.CrossRef
11.
go back to reference Neff AM, Yu J, Taylor RN, Bagchi IC, Bagchi MK. Insulin signaling via progesterone-regulated insulin receptor substrate 2 is critical for human uterine decidualization. Endocrinol (United States). 2020;161(1):bqz021. Neff AM, Yu J, Taylor RN, Bagchi IC, Bagchi MK. Insulin signaling via progesterone-regulated insulin receptor substrate 2 is critical for human uterine decidualization. Endocrinol (United States). 2020;161(1):bqz021.
12.
go back to reference Frolova AI, Moley KH. Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine receptivity. Endocrinology. 2011;152(5):2123–8.CrossRef Frolova AI, Moley KH. Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine receptivity. Endocrinology. 2011;152(5):2123–8.CrossRef
13.
go back to reference Ujvari D, Jakson I, Babayeva S, Salamon D, Rethi B, Gidlöf S, et al. Dysregulation of in vitro decidualization of human endometrial stromal cells by insulin via transcriptional inhibition of forkhead box protein O1. PLoS One. 2017;12(1):e0171004. Ujvari D, Jakson I, Babayeva S, Salamon D, Rethi B, Gidlöf S, et al. Dysregulation of in vitro decidualization of human endometrial stromal cells by insulin via transcriptional inhibition of forkhead box protein O1. PLoS One. 2017;12(1):e0171004.
14.
go back to reference Palomba S, De Wilde MA, Falbo A, Koster MPH, Battista G, Sala L, et al.Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21(5):575–92. Palomba S, De Wilde MA, Falbo A, Koster MPH, Battista G, Sala L, et al.Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21(5):575–92.
15.
go back to reference Ke RW. Endocrine basis for recurrent pregnancy loss. Obstet Gynecol Clin North Am. 2014;41(1):103-12. Ke RW. Endocrine basis for recurrent pregnancy loss. Obstet Gynecol Clin North Am. 2014;41(1):103-12.
16.
go back to reference Ujvari D, Hulchiy M, Calaby A, Nybacka A, Byström B, Hirschberg AL. Lifestyle intervention up-regulates gene and protein levels of molecules involved in insulin signaling in the endometrium of overweight/obese women with polycystic ovary syndrome. Hum Reprod. 2014;29(7):1526–35.CrossRef Ujvari D, Hulchiy M, Calaby A, Nybacka A, Byström B, Hirschberg AL. Lifestyle intervention up-regulates gene and protein levels of molecules involved in insulin signaling in the endometrium of overweight/obese women with polycystic ovary syndrome. Hum Reprod. 2014;29(7):1526–35.CrossRef
17.
go back to reference Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133-223. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133-223.
18.
go back to reference Sargeant RJ, Pâquet MR. Effect of insulin on the rates of synthesis and degradation of GLUT1 and GLUT4 glucose transporters in 3T3-L1 adipocytes. Biochem J. 1993;290(Pt 3):913–9.CrossRef Sargeant RJ, Pâquet MR. Effect of insulin on the rates of synthesis and degradation of GLUT1 and GLUT4 glucose transporters in 3T3-L1 adipocytes. Biochem J. 1993;290(Pt 3):913–9.CrossRef
19.
go back to reference Takano M, Lu Z, Goto T, Fusi L, Higham J, Francis J, et al. Transcriptional cross talk between the forkhead transcription factor forkhead box O1A and the progesterone receptor coordinates cell cycle regulation and differentiation in human endometrial stromal cells. Mol Endocrinol. 2007;21(10):2334–49.CrossRef Takano M, Lu Z, Goto T, Fusi L, Higham J, Francis J, et al. Transcriptional cross talk between the forkhead transcription factor forkhead box O1A and the progesterone receptor coordinates cell cycle regulation and differentiation in human endometrial stromal cells. Mol Endocrinol. 2007;21(10):2334–49.CrossRef
20.
go back to reference Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol. 2015;29(4):498-506. Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol. 2015;29(4):498-506.
21.
go back to reference Liu L, Tong X, Jiang L, Li TC, Zhou F, Zhang S. A comparison of the miscarriage rate between women with and without polycystic ovarian syndrome undergoing IVF treatment. Eur J Obstet Gynecol Reprod Biol. 2014;176:178-82. Liu L, Tong X, Jiang L, Li TC, Zhou F, Zhang S. A comparison of the miscarriage rate between women with and without polycystic ovarian syndrome undergoing IVF treatment. Eur J Obstet Gynecol Reprod Biol. 2014;176:178-82.
22.
go back to reference Kjerulff LE, Sanchez-Ramos L, Duffy D. Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis. Am J Obstet Gynecol. 2011;204(6):558.e1–6. Kjerulff LE, Sanchez-Ramos L, Duffy D. Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis. Am J Obstet Gynecol. 2011;204(6):558.e1–6.
23.
go back to reference Dutton H, Borengasser SJ, Gaudet LM, Barbour LA, Keely EJ. Obesity in pregnancy: optimizing outcomes for mom and baby. Med Clin N Am. 2018;102(1):87-106. Dutton H, Borengasser SJ, Gaudet LM, Barbour LA, Keely EJ. Obesity in pregnancy: optimizing outcomes for mom and baby. Med Clin N Am. 2018;102(1):87-106.
24.
go back to reference Jin Z, Jin Y, Kumar-Mendu S, Degerman E, Groop L, Birnir B. Insulin reduces neuronal excitability by turning on GABAA channels that generate tonic current. PLoS One. 2011;6(1):e16188. Jin Z, Jin Y, Kumar-Mendu S, Degerman E, Groop L, Birnir B. Insulin reduces neuronal excitability by turning on GABAA channels that generate tonic current. PLoS One. 2011;6(1):e16188.
25.
go back to reference Qiao L, Li Y, Sun S. Insulin exacerbates inflammation in fibroblast-like Synoviocytes. Inflammation. 2020;43(3):916-936. Qiao L, Li Y, Sun S. Insulin exacerbates inflammation in fibroblast-like Synoviocytes. Inflammation. 2020;43(3):916-936.
26.
go back to reference Ribeiro M, López de Figueroa P, Blanco FJ, Mendes AF, Caramés B. Insulin decreases autophagy and leads to cartilage degradation. Osteoarthr Cartil. 2016;24(4):731-9. Ribeiro M, López de Figueroa P, Blanco FJ, Mendes AF, Caramés B. Insulin decreases autophagy and leads to cartilage degradation. Osteoarthr Cartil. 2016;24(4):731-9.
27.
go back to reference Trujeque-Ramos S, Castillo-Rolón D, Galarraga E, Tapia D, Arenas-López G, Mihailescu S, et al. Insulin regulates GABAA receptor-mediated tonic currents in the prefrontal cortex. Front Neurosci. 2018;12:345. Trujeque-Ramos S, Castillo-Rolón D, Galarraga E, Tapia D, Arenas-López G, Mihailescu S, et al. Insulin regulates GABAA receptor-mediated tonic currents in the prefrontal cortex. Front Neurosci. 2018;12:345.
28.
go back to reference Agardh CD, Lesniak MA, Gerritsen GC, Roth J. The influence of plasma insulin concentrations on tissue insulin levels in rodents: a study of the diabetic chinese hamster and the Ob Ob mouse. Metabolism. 1986;35(3):244-9. Agardh CD, Lesniak MA, Gerritsen GC, Roth J. The influence of plasma insulin concentrations on tissue insulin levels in rodents: a study of the diabetic chinese hamster and the Ob Ob mouse. Metabolism. 1986;35(3):244-9.
Metadata
Title
Insulin regulation of solute carrier family 2 member 1 (glucose transporter 1) expression and glucose uptake in decidualizing human endometrial stromal cells: an in vitro study
Authors
Ivika Jakson
Dorina Ujvari
Sebastian Brusell Gidlöf
Angelica Lindén Hirschberg
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
Insulins
Insulins
Published in
Reproductive Biology and Endocrinology / Issue 1/2020
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-020-00674-0

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