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Insulin and the Placenta in GDM

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Gestational Diabetes During and After Pregnancy

Abstract

Placental development and function are tightly regulated by endocrine, paracrine, and autocrine factors present in the maternal and the fetal circulation and in the placenta. Gestational diabetes (GDM) is associated with a derangement of the concentration of several hormones, cytokines, metabolites, and growth factors in both circulations that may subsequently alter placental morphology and function. One of these is the peptide hormone insulin, which exerts pleiotropic effects on target cells. The placenta is very rich in receptors for insulin and insulin-like growth factors (IGFs) and is therefore susceptible to their concentration changes. This chapter describes general placental alterations in GDM and particularly focuses on the effects of insulin and its signalling components on the placenta.

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References

  1. Kalhan SC, Schwartz R, Adam PA. Placental barrier to human insulin-I125 in insulin-dependent diabetic mothers. J Clin Endocrinol Metab. 1975;40(1):139-142.

    Article  CAS  PubMed  Google Scholar 

  2. Menon RK et al. Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. Its role in fetal macrosomia. N Engl J Med. 1990;323(5):309-315.

    Article  CAS  PubMed  Google Scholar 

  3. Weirich G et al. Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines. Biol Chem. 2008;389(11):1441-1445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Martikainen A et al. Disease-associated antibodies in offspring of mothers with IDDM. Diabetes. 1996;45(12):1706-1710.

    Article  CAS  PubMed  Google Scholar 

  5. Weiss PA et al. Anti-insulin antibodies and birth weight in pregnancies complicated by diabetes. Early Hum Dev. 1998;53(2):145-154.

    Article  CAS  PubMed  Google Scholar 

  6. Velcovsky HG, Federlin KF. Insulin-specific IgG and IgE antibody response in type I diabetic subjects exclusively treated with human insulin (recombinant DNA). Diabetes Care. 1982; 5(suppl 2):126-128.

    Google Scholar 

  7. Jovanovic L et al. Metabolic and immunologic effects of insulin lispro in gestational diabetes. Diabetes Care. 1999;22(9):1422-1427.

    Article  CAS  PubMed  Google Scholar 

  8. McCance DR et al. Evaluation of insulin antibodies and placental transfer of insulin aspart in pregnant women with type 1 diabetes mellitus. Diabetologia. 2008;51(11):2141-2143.

    Article  CAS  PubMed  Google Scholar 

  9. Nanovskaya TN et al. Transfer of metformin across the dually perfused human placental lobule. Am J Obstet Gynecol. 2006;195(4):1081-1085.

    Article  CAS  PubMed  Google Scholar 

  10. Nicholson W et al. Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: a systematic review. Obstet Gynecol. 2009;113(1):193-205.

    Article  PubMed  Google Scholar 

  11. Hiles RA, Bawdon RE, Petrella EM. Ex vivo human placental transfer of the peptides pramlintide and exenatide (synthetic exendin-4). Hum Exp Toxicol. 2003;22(12):623-628.

    Article  CAS  PubMed  Google Scholar 

  12. Feig DS, Briggs GG, Koren G. Oral antidiabetic agents in pregnancy and lactation: a paradigm shift? Ann Pharmacother. 2007;41(7):1174-1180.

    Article  CAS  PubMed  Google Scholar 

  13. Desoye G, Barnea ER, Shurz-Swirsky R. Increase in insulin binding and inhibition of the decrease in the phospholipid content of human term placental homogenates in culture by the sulfonylurea glipizide. Biochem Pharmacol. 1993;46(9):1585-1590.

    Article  CAS  PubMed  Google Scholar 

  14. Desoye G, Hofmann HH, Weiss PA. Insulin binding to trophoblast plasma membranes and placental glycogen content in well-controlled gestational diabetic women treated with diet or insulin, in well-controlled overt diabetic patients and in healthy control subjects. Diabetologia. 1992;35(1):45-55.

    Article  CAS  PubMed  Google Scholar 

  15. Desoye G et al. Insulin receptors in syncytiotrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern. Histochemistry. 1994;101(4):277-285.

    Article  CAS  PubMed  Google Scholar 

  16. Hiden U, et al. Insulin and the IGF system in the human placenta of normal and diabetic pregnancies. J Anat. 2009;215:60-68.

    Google Scholar 

  17. Matsuzawa Y, Funahashi T, Nakamura T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann N Y Acad Sci. 1999;892:146-154.

    Article  CAS  PubMed  Google Scholar 

  18. Ategbo JM et al. Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J Clin Endocrinol Metab. 2006;91(10):4137-4143.

    Article  CAS  PubMed  Google Scholar 

  19. Vitoratos N et al. Maternal plasma leptin levels and their relationship to insulin and glucose in gestational-onset diabetes. Gynecol Obstet Invest. 2001;51(1):17-21.

    Article  CAS  PubMed  Google Scholar 

  20. Lea RG et al. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod. 2000;6(8):763-769.

    Article  CAS  PubMed  Google Scholar 

  21. Worda C et al. Decreased plasma adiponectin concentrations in women with gestational diabetes mellitus. Am J Obstet Gynecol. 2004;191(6):2120-2124.

    Article  CAS  PubMed  Google Scholar 

  22. Ng PC et al. Plasma ghrelin and resistin concentrations are suppressed in infants of insulin-dependent diabetic mothers. J Clin Endocrinol Metab. 2004;89(11):5563-5568.

    Article  CAS  PubMed  Google Scholar 

  23. Desoye G, Shafrir E. The human placenta in diabetic pregnancy. Diabetes Rev. 1996;4:70-89.

    Google Scholar 

  24. Desoye G, Kaufmann P. The human placenta in diabetes. In: Porta M, Matschinsky FM, eds. Diabetology of Pregnancy. Basel:Karger; 2006:94-109.

    Google Scholar 

  25. Taricco E et al. Foetal and placental weights in relation to maternal characteristics in gestational diabetes. Placenta. 2003;24(4):343-347.

    Article  CAS  PubMed  Google Scholar 

  26. Durnwald C et al. Evaluation of body composition of large-for-gestational-age infants of women with gestational diabetes mellitus compared with women with normal glucose tolerance levels. Am J Obstet Gynecol. 2004;191(3):804-808.

    Article  CAS  PubMed  Google Scholar 

  27. Mayhew TM et al. Growth and maturation of villi in placentae from well-controlled diabetic women. Placenta. 1994;15(1):57-65.

    Article  CAS  PubMed  Google Scholar 

  28. Mandl M et al. Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models. Histochem Cell Biol. 2002;117(5):391-399.

    Article  CAS  PubMed  Google Scholar 

  29. Hiden U et al. MT1-MMP expression in first-trimester placental tissue is upregulated in type 1 diabetes as a result of elevated insulin and tumor necrosis factor-alpha levels. Diabetes. 2008;57(1):150-157.

    Article  CAS  PubMed  Google Scholar 

  30. Madazli R et al. The incidence of placental abnormalities, maternal and cord plasma malondialdehyde and vascular endothelial growth factor levels in women with gestational diabetes mellitus and nondiabetic controls. Gynecol Obstet Invest. 2008;65(4):227-232.

    Article  CAS  PubMed  Google Scholar 

  31. Black SM, Devol JM, Wedgwood S. Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation. Am J Physiol Cell Physiol. 2008;294(1):C345-C354.

    Article  CAS  PubMed  Google Scholar 

  32. Josko J, Mazurek M. Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis. Med Sci Monit. 2004;10(4): RA89-RA98.

    Google Scholar 

  33. Jirkovska M et al. Topological properties and spatial organization of villous capillaries in normal and diabetic placentas. J Vasc Res. 2002;39(3):268-278.

    Article  PubMed  Google Scholar 

  34. Radaelli T et al. Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes. 2003;52(12):2951-2958.

    Article  CAS  PubMed  Google Scholar 

  35. Enquobahrie DA, et al. Global placental gene expression in gestational diabetes mellitus. Am J Obstet Gynecol. 2009;200(2):206 e1-e13.

    Google Scholar 

  36. Hiden U et al. Insulin control of placental gene expression shifts from mother to foetus over the course of pregnancy. Diabetologia. 2006;49(1):123-131.

    Article  CAS  PubMed  Google Scholar 

  37. Osmond DT et al. Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients. Diabetologia. 2001;44(9):1133-1139.

    Article  CAS  PubMed  Google Scholar 

  38. Osmond DT et al. Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation. Diabetologia. 2000;43(5):576-582.

    Article  CAS  PubMed  Google Scholar 

  39. Radaelli T, et al. Oxygenation, acid-base-balance and glucose levels in fetuses from gestational diabetic pregnancies. J Soc Gynecol Invest. 2005;2(suppl):221A.

    Google Scholar 

  40. Jansson T et al. Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes. 2002;51(7):2214-2219.

    Article  CAS  PubMed  Google Scholar 

  41. Dicke JM, Henderson GI. Placental amino acid uptake in normal and complicated pregnancies. Am J Med Sci. 1988;295(3):223-227.

    Article  CAS  PubMed  Google Scholar 

  42. Kuruvilla AG et al. Altered activity of the system A amino acid transporter in microvillous membrane vesicles from placentas of macrosomic babies born to diabetic women. J Clin Invest. 1994;94(2):689-695.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Merzouk H et al. Changes in serum lipid and lipoprotein concentrations and compositions at birth and after 1 month of life in macrosomic infants of insulin-dependent diabetic mothers. Eur J Pediatr. 1999;158(9):750-756.

    Article  CAS  PubMed  Google Scholar 

  44. Couch SC et al. Elevated lipoprotein lipids and gestational hormones in women with diet-treated gestational diabetes mellitus compared to healthy pregnant controls. J Diabetes Complications. 1998;12(1):1-9.

    Article  CAS  PubMed  Google Scholar 

  45. Malassine A et al. Acetylated low density lipoprotein endocytosis by human syncytiotrophoblast in culture. Placenta. 1990;11(2):191-204.

    Article  CAS  PubMed  Google Scholar 

  46. Wadsack C et al. Selective cholesteryl ester uptake from high density lipoprotein by human first trimester and term villous trophoblast cells. Placenta. 2003;24(2–3):131-143.

    Article  CAS  PubMed  Google Scholar 

  47. Gauster M et al. Dysregulation of placental endothelial lipase and lipoprotein lipase in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab. 2007;92(6):2256-2263.

    Article  CAS  PubMed  Google Scholar 

  48. Cunningham P, McDermott L. Long chain PUFA transport in human term placenta. J Nutr. 2009;139(4):636-639.

    Article  CAS  PubMed  Google Scholar 

  49. Herrera E et al. Maternal lipid metabolism and placental lipid transfer. Horm Res. 2006;65 (suppl 3):59-64.

    Article  CAS  PubMed  Google Scholar 

  50. Bitsanis D et al. Gestational diabetes mellitus enhances arachidonic and docosahexaenoic acids in placental phospholipids. Lipids. 2006;41(4):341-346.

    Article  CAS  PubMed  Google Scholar 

  51. Thomas B et al. Plasma AA and DHA levels are not compromised in newly diagnosed gestational diabetic women. Eur J Clin Nutr. 2004;58(11):1492-1497.

    Article  CAS  PubMed  Google Scholar 

  52. Thomas BA et al. Plasma fatty acids of neonates born to mothers with and without gestational diabetes. Prostaglandins Leukot Essent Fatty Acids. 2005;72(5):335-341.

    Article  CAS  PubMed  Google Scholar 

  53. Ortega-Senovilla H et al. Gestational diabetes mellitus upsets the proportion of fatty acids in umbilical arterial but not venous plasma. Diabetes Care. 2009;32(1):120-122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Madsen H, Ditzel J. Red cell 2, 3-diphosphoglycerate and hemoglobin-oxygen affinity during diabetic pregnancy. Acta Obstet Gynecol Scand. 1984;63(5):403-406.

    Article  CAS  PubMed  Google Scholar 

  55. Nylund L et al. Uteroplacental blood flow in diabetic pregnancy: measurements with indium 113m and a computer-linked gamma camera. Am J Obstet Gynecol. 1982;144(3):298-302.

    CAS  PubMed  Google Scholar 

  56. al-Okail MS, al-Attas OS. Histological changes in placental syncytiotrophoblasts of poorly controlled gestational diabetic patients. Endocr J. 1994;41(4):355-360.

    Google Scholar 

  57. Leushner JR et al. Analysis of the collagens of diabetic placental villi. Cell Mol Biol. 1986;32(1):27-35.

    CAS  PubMed  Google Scholar 

  58. Guyda HJ. Metabolic effects of growth factors and polycyclic aromatic hydrocarbons on cultured human placental cells of early and late gestation. J Clin Endocrinol Metab. 1991; 72(3):718-723.

    Article  CAS  PubMed  Google Scholar 

  59. Karl PI, Alpy KL, Fisher SE. Amino acid transport by the cultured human placental trophoblast: effect of insulin on AIB transport. Am J Physiol. 1992;262(4 pt 1):C834-C839.

    CAS  PubMed  Google Scholar 

  60. Hochberg Z et al. Insulin regulates placental lactogen and estradiol secretion by cultured human term trophoblast. J Clin Endocrinol Metab. 1983;57(6):1311-1313.

    Article  CAS  PubMed  Google Scholar 

  61. Perlman R et al. The effect of inhibitors on insulin regulation of hormone secretion by cultured human trophoblast. Mol Cell Endocrinol. 1985;43(1):77-82.

    Article  CAS  PubMed  Google Scholar 

  62. Nestler JE et al. Insulin mediators are the signal transduction system responsible for insulin’s actions on human placental steroidogenesis. Endocrinology. 1991;129(6):2951-2956.

    Article  CAS  PubMed  Google Scholar 

  63. Olszewski J, Szczurowicz A, Wojcikowski C. Changes in levels of human placenta lactogen (hPL), progesterone, and estriol in blood serum and estrogens in urine during gestational diabetes mellitus. Ginekol Pol. 1995;66(3):145-150.

    CAS  PubMed  Google Scholar 

  64. Grigorakis SI et al. Hormonal parameters in gestational diabetes mellitus during the third trimester: high glucagon levels. Gynecol Obstet Invest. 2000;49(2):106-109.

    Article  CAS  PubMed  Google Scholar 

  65. Montelongo A et al. Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women. Diabetes. 1992;41(12):1651-1659.

    Article  CAS  PubMed  Google Scholar 

  66. Zeck W et al. Regulation of placental growth hormone secretion in a human trophoblast model–the effects of hormones and adipokines. Pediatr Res. 2008;63(4):353-357.

    Article  CAS  PubMed  Google Scholar 

  67. Barbour LA et al. Human placental growth hormone causes severe insulin resistance in transgenic mice. Am J Obstet Gynecol. 2002;186(3):512-517.

    Article  CAS  PubMed  Google Scholar 

  68. Elchalal U et al. Insulin and fatty acids regulate the expression of the fat droplet-associated protein adipophilin in primary human trophoblasts. Am J Obstet Gynecol. 2005;193(5):1716-1723.

    Article  CAS  PubMed  Google Scholar 

  69. Shafrir E, Barash V. Placental function in maternal-fetal fat transport in diabetes. Biol Neonate. 1987;51(2):102-112.

    Article  CAS  PubMed  Google Scholar 

  70. Hiden U, et al. Insulin action on the human placental endothelium in normal and diabetic pregnancy. Curr Vasc Pharmacol. 2009;7:460-466.

    Google Scholar 

  71. Jiang ZY et al. Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth factor expression in vascular cells and angiogenesis. J Biol Chem. 2003;278(34):31964-31971.

    Article  CAS  PubMed  Google Scholar 

  72. Colomiere M et al. Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus. Eur J Endocrinol. 2009;160(4):567-578.

    Article  CAS  PubMed  Google Scholar 

  73. Duran-Garcia S, Nieto JG, Cabello AM. Effect of gestational diabetes on insulin receptors in human placenta. Diabetologia. 1979;16(2):87-91.

    Article  CAS  PubMed  Google Scholar 

  74. al-Attas OS, al-Okail MS. Features of insulin receptor interaction in placenta from normal, overt and poorly controlled gestational diabetic patients. Mol Cell Biochem. 1993;126(2):135-142.

    Google Scholar 

  75. Roy MS et al. The ovine corticotropin-releasing hormone-stimulation test in type I diabetic patients and controls: suggestion of mild chronic hypercortisolism. Metabolism. 1993; 42(6):696-700.

    Article  CAS  PubMed  Google Scholar 

  76. Tomlinson JW et al. Impaired glucose tolerance and insulin resistance are associated with increased adipose 11beta-hydroxysteroid dehydrogenase type 1 expression and elevated hepatic 5alpha-reductase activity. Diabetes. 2008;57(10):2652-2660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mamula PW et al. Regulating insulin-receptor-gene expression by differentiation and hormones. Diabetes Care. 1990;13(3):288-301.

    Article  CAS  PubMed  Google Scholar 

  78. Barbour LA, et al. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care. 2007;30(suppl 2):S112-S119.

    Google Scholar 

  79. Kautzky-Willer A et al. Increased plasma leptin in gestational diabetes. Diabetologia. 2001;44(2):164-172.

    Article  CAS  PubMed  Google Scholar 

  80. Howard JK, Flier JS. Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol Metab. 2006;17(9):365-371.

    Article  CAS  PubMed  Google Scholar 

  81. Kirwan JP et al. TNF-alpha is a predictor of insulin resistance in human pregnancy. Diabetes. 2002;51(7):2207-2213.

    Article  CAS  PubMed  Google Scholar 

  82. Tomazic M et al. Comparison of alterations in insulin signalling pathway in adipocytes from Type II diabetic pregnant women and women with gestational diabetes mellitus. Diabetologia. 2002;45(4):502-508.

    Article  CAS  PubMed  Google Scholar 

  83. Shao J et al. Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese women with gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM. Diabetes. 2000;49(4):603-610.

    Article  CAS  PubMed  Google Scholar 

  84. Alonso A et al. Effects of gestational diabetes mellitus on proteins implicated in insulin signaling in human placenta. Gynecol Endocrinol. 2006;22(9):526-535.

    Article  CAS  PubMed  Google Scholar 

  85. Van Obberghen E et al. Surfing the insulin signaling web. Eur J Clin Invest. 2001;31(11):966-977.

    Article  PubMed  Google Scholar 

  86. Withers DJ et al. Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 1998; 391(6670):900-904.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria

    G. Desoye

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  1. Ursula Hiden
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  2. G. Desoye
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Correspondence to G. Desoye .

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Editors and Affiliations

  1. University of Michigan Health System, Ann Arbor, Michigan, USA

    Catherine Kim

  2. Kaiser Permanente, Division of Research Clinics Kaiser Permanente, Oakland, California, USA

    Assiamira Ferrara

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Hiden, U., Desoye, G. (2010). Insulin and the Placenta in GDM. In: Kim, C., Ferrara, A. (eds) Gestational Diabetes During and After Pregnancy. Springer, London. https://doi.org/10.1007/978-1-84882-120-0_7

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  • DOI: https://doi.org/10.1007/978-1-84882-120-0_7

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