{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:07:59Z","timestamp":1789168079120,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)]","doi-asserted-by":"publisher","award":["288034826\u2014IRTG 2251"],"award-info":[{"award-number":["288034826\u2014IRTG 2251"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TUD Dresden University of Technology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gestational Diabetes Mellitus (GDM) increases the long-term risk for metabolic and cardiovascular diseases in the offspring. However, the underlying mechanisms are not well understood. This study investigates the impact of GDM on fetoplacental vascular function and molecular mechanisms underlying endothelial dysfunction. Clinical data and tissue samples were collected from normoglycemic (NG, n = 33) and GDM (n = 19) pregnancies. Offspring in the GDM group were delivered earlier, had a larger placental size, and had a reduced placental efficiency. Functional analysis using a Mulvany myograph demonstrated a significant impairment of insulin-mediated vasodilation in fetoplacental vessels of GDM patients compared to NG controls. This vascular dysfunction was associated with a reduction in total insulin receptor protein expression. Further investigation revealed an impaired PI3K\/AKT\/eNOS signaling pathway, as endothelial cells from GDM pregnancies showed a deficient insulin-induced phosphorylation of AKT. These results indicate that maternal GDM induces insulin resistance and endothelial dysfunction in the fetoplacental vasculature through impairment of the AKT\/eNOS pathway, providing a key mechanism for its adverse neonatal outcomes and the increased lifelong cardiovascular risk in the offspring.<\/jats:p>","DOI":"10.3390\/ijms262311507","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:31:52Z","timestamp":1764261112000},"page":"11507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Maternal Gestational Diabetes Impairs Fetoplacental Insulin-Induced Vasodilation via AKT\/eNOS Pathway and Reduces Placental Efficiency"],"prefix":"10.3390","volume":"26","author":[{"given":"Clara M.","family":"Hengst","sequence":"first","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria de Leyre","family":"Villar-Ballesteros","sequence":"additional","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"},{"name":"Department of Women & Children\u2019s Health, School of Life Course Sciences, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-1807","authenticated-orcid":false,"given":"Heike","family":"Brendel","sequence":"additional","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindy","family":"Giebe","sequence":"additional","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6421-9752","authenticated-orcid":false,"given":"Coy","family":"Brunssen","sequence":"additional","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8461-5605","authenticated-orcid":false,"given":"Alexander","family":"Fr\u00fchauf","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Feto\/neonatal Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-1178","authenticated-orcid":false,"given":"Cahit","family":"Birdir","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Feto\/neonatal Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-4307","authenticated-orcid":false,"given":"Paul D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Women & Children\u2019s Health, School of Life Course Sciences, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Poston","sequence":"additional","affiliation":[{"name":"Department of Women & Children\u2019s Health, School of Life Course Sciences, King\u2019s College London, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-9736","authenticated-orcid":false,"given":"Henning","family":"Morawietz","sequence":"additional","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, September 01). Meeting of the Guideline Development Group for the Monitoring and Management of Hyperglycaemia in Pregnancy. Available online: https:\/\/www.who.int\/news\/item\/28-04-2025-meeting-of-the-guideline-development-group-for-the-monitoring-and-management-of-hyperglycaemia-in-pregnancy."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1007\/s11154-025-09987-0","article-title":"Trends in gestational diabetes prevalence in China from 1990 to 2024: A systematic review and meta-analysis","volume":"26","author":"Wu","year":"2025","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_3","unstructured":"International Diabetes Federation (2025). IDF Diabetes Atlas, International Diabetes Federation. [11th ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S2213-8587(20)30161-3","article-title":"Gestational diabetes: Opportunities for improving maternal and child health","volume":"8","author":"Saravanan","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0140-6736(24)00825-0","article-title":"Epidemiology and management of gestational diabetes","volume":"404","author":"Sweeting","year":"2024","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1017\/S2040174419000850","article-title":"Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis","volume":"11","author":"Pathirana","year":"2020","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s12933-024-02416-7","article-title":"Gestational diabetes mellitus and development of intergenerational overall and subtypes of cardiovascular diseases: A systematic review and meta-analysis","volume":"23","author":"Chen","year":"2024","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"l6398","DOI":"10.1136\/bmj.l6398","article-title":"Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: Population based cohort study with 40 years of follow-up","volume":"367","author":"Yu","year":"2019","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1055\/s-0031-1275515","article-title":"Placental dysfunction and fetal programming: The importance of placental size, shape, histopathology, and molecular composition","volume":"29","author":"Longtine","year":"2011","journal-title":"Semin. Reprod. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1017\/S2040174415001300","article-title":"The programming of cardiovascular disease","volume":"6","author":"Thornburg","year":"2015","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/pd.6572","article-title":"Interdependence of placenta and fetal cardiac development","volume":"44","author":"Leon","year":"2024","journal-title":"Prenat. Diagn."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e1555","DOI":"10.1002\/wsbm.1555","article-title":"The birth of cardiac disease: Mechanisms linking gestational diabetes mellitus and early onset of cardiovascular disease in offspring","volume":"14","author":"Tocantins","year":"2022","journal-title":"WIREs Mech. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Zhang, Y., Huang, S., Li, M., Li, L., Qi, L., He, Y., Xu, Z., and Tang, J. (2025). Influence of gestational diabetes mellitus on the cardiovascular system and its underlying mechanisms. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1474643"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1093\/cvr\/cvab280","article-title":"Down-regulation of AMPK\/PPAR\u03b4 signalling promotes endoplasmic reticulum stress-induced endothelial dysfunction in adult rat offspring exposed to maternal diabetes","volume":"118","author":"Luo","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1161\/01.CIR.0000139843.05436.A0","article-title":"Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring","volume":"110","author":"Khan","year":"2004","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Contreras-Duarte, S., Carvajal, L., Garchitorena, M.J., Subiabre, M., Fuenzalida, B., Cantin, C., Farias, M., and Leiva, A. (2020). Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women s Weight: Possible Impact on Feto-Placental Vascular Function. Nutrients, 12.","DOI":"10.3390\/nu12020506"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00424-009-0767-7","article-title":"Molecular mechanisms underlying the activation of eNOS","volume":"459","author":"Fleming","year":"2010","journal-title":"Pflug. Arch."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Subiabre, M., Villalobos-Labra, R., Silva, L., Fuentes, G., Toledo, F., and Sobrevia, L. (2020). Role of insulin, adenosine, and adipokine receptors in the foetoplacental vascular dysfunction in gestational diabetes mellitus. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2018.12.021"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kolb, H., Kempf, K., R\u00f6hling, M., and Martin, S. (2020). Insulin: Too much of a good thing is bad. BMC Med., 18.","DOI":"10.1186\/s12916-020-01688-6"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"H1231","DOI":"10.1152\/ajpheart.00537.2022","article-title":"New insights into mechanisms of endothelial insulin resistance in type 2 diabetes","volume":"323","author":"Padilla","year":"2022","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4093\/dmj.2017.41.6.457","article-title":"Adipokines and Insulin Resistance According to Characteristics of Pregnant Women with Gestational Diabetes Mellitus","volume":"41","author":"Jeon","year":"2017","journal-title":"Diabetes Metab. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mirabelli, M., Tocci, V., Donnici, A., Giuliano, S., Sarnelli, P., Salatino, A., Greco, M., Puccio, L., Chiefari, E., and Foti, D.P. (2023). Maternal Preconception Body Mass Index Overtakes Age as a Risk Factor for Gestational Diabetes Mellitus. J. Clin. Med., 12.","DOI":"10.3390\/jcm12082830"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1007\/s00125-015-3726-1","article-title":"Sex of the baby and risk of gestational diabetes mellitus in the mother: A systematic review and meta-analysis","volume":"58","author":"Jaskolka","year":"2015","journal-title":"Diabetologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"844","DOI":"10.2337\/dc14-2551","article-title":"Fetal sex and maternal risk of gestational diabetes mellitus: The impact of having a boy","volume":"38","author":"Retnakaran","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00592-021-01836-1","article-title":"The impact of fetal sex on risk factors for gestational diabetes and related adverse pregnancy outcomes","volume":"59","author":"Seghieri","year":"2022","journal-title":"Acta Diabetol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/ijgo.70185","article-title":"Effects of gestational diabetes mellitus on offspring: A literature review","volume":"171","author":"Li","year":"2025","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1111\/aogs.12509","article-title":"Placental weight and placental weight to birthweight ratio in relation to Apgar score at birth: A population study of 522 360 singleton pregnancies","volume":"93","author":"Eskild","year":"2014","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"F21","DOI":"10.1152\/ajprenal.00383.2023","article-title":"Early-life exposures and long-term health: Adverse gestational environments and the programming of offspring renal and vascular disease","volume":"327","author":"Oulerich","year":"2024","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Poston, L., Godfrey, K.M., Gluckman, P.D., and Hanson, M.A. (2022). The Role of the Placenta in DOHaD. Developmental Origins of Health and Disease, Cambridge University Press.","DOI":"10.1017\/9781009272254"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/aogs.12104","article-title":"Placental weight relative to birthweight in pregnancies with maternal diabetes mellitus","volume":"92","author":"Haavaldsen","year":"2013","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.placenta.2020.10.013","article-title":"The role of obesity and gestational diabetes on placental size and fetal oxygenation","volume":"103","author":"Bianchi","year":"2021","journal-title":"Placenta"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lean, S.C., Heazell, A.E.P., Dilworth, M.R., Mills, T.A., and Jones, R.L. (2017). Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09814-w"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1530\/JOE-18-0093","article-title":"Chorionic somatomammotropin impacts early fetal growth and placental gene expression","volume":"237","author":"Jeckel","year":"2018","journal-title":"J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1210\/jc.2010-0023","article-title":"Differential expression profile of growth hormone\/chorionic somatomammotropin genes in placenta of small- and large-for-gestational-age newborns","volume":"95","author":"Vaas","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rassie, K., Giri, R., Joham, A.E., Teede, H., and Mousa, A. (2022). Human Placental Lactogen in Relation to Maternal Metabolic Health and Fetal Outcomes: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415621"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.mce.2012.02.009","article-title":"Differential placental expression profile of human Growth Hormone\/Chorionic Somatomammotropin genes in pregnancies with pre-eclampsia and gestational diabetes mellitus","volume":"355","author":"Mannik","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_37","first-page":"685","article-title":"Diabetes and pregnancy; blood sugar of newborn infants during fasting and glucose administration","volume":"114","author":"Pedersen","year":"1952","journal-title":"Ugeskr. Laeger."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1172\/JCI118709","article-title":"Obesity\/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance","volume":"97","author":"Steinberg","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41419-023-05935-5","article-title":"Vascular nitric oxide resistance in type 2 diabetes","volume":"14","author":"Bahadoran","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1161\/01.CIR.88.6.2510","article-title":"Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus","volume":"88","author":"Johnstone","year":"1993","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"H793","DOI":"10.1152\/ajpheart.00223.2024","article-title":"Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes","volume":"327","author":"Schwartz","year":"2024","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00424-024-03028-6","article-title":"Characterization of human placental fetal vessels in gestational diabetes mellitus","volume":"477","author":"Carstens","year":"2025","journal-title":"Pflug. Arch."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E8478","DOI":"10.1073\/pnas.1710625114","article-title":"Endothelial insulin receptors differentially control insulin signaling kinetics in peripheral tissues and brain of mice","volume":"114","author":"Konishi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e86574","DOI":"10.1172\/jci.insight.86574","article-title":"Insulin decreases atherosclerosis by inducing endothelin receptor B expression","volume":"1","author":"Park","year":"2016","journal-title":"JCI Insight"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/jmcb\/mjab024","article-title":"Diabetes pathogenesis and management: The endothelium comes of age","volume":"13","author":"Love","year":"2021","journal-title":"J. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1161\/CIRCULATIONAHA.105.563213","article-title":"Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms","volume":"113","author":"Kim","year":"2006","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Casanello, P., Schneider, D., Herrera, E.A., Uauy, R., and Krause, B.J. (2014). Endothelial heterogeneity in the umbilico-placental unit: DNA methylation as an innuendo of epigenetic diversity. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00049"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.placenta.2012.02.006","article-title":"Role of arginase-2 and eNOS in the differential vascular reactivity and hypoxia-induced endothelial response in umbilical arteries and veins","volume":"33","author":"Krause","year":"2012","journal-title":"Placenta"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, J.J., Wang, X., Li, Q., Huang, H., Zheng, Q.L., Yao, Q., and Zhang, J. (2023). Feto-placental endothelial dysfunction in Gestational Diabetes Mellitus under dietary or insulin therapy. BMC Endocr. Disord., 23.","DOI":"10.1186\/s12902-023-01305-6"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sissaoui, S., Egginton, S., Ting, L., Ahmed, A., and Hewett, P.W. (2021). Hyperglycaemia up-regulates placental growth factor (PlGF) expression and secretion in endothelial cells via suppression of PI3 kinase-Akt signalling and activation of FOXO1. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-95511-8"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1172\/JCI11235","article-title":"Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site","volume":"108","author":"Du","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"104076","DOI":"10.1016\/j.mvr.2020.104076","article-title":"Exposure to maternal diabetes induces endothelial dysfunction and hypertension in adult male rat offspring","volume":"133","author":"Yu","year":"2021","journal-title":"Microvasc. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000291514","article-title":"Nitric oxide synthase activity in umbilical and placental vascular tissue of gestational diabetic pregnancies","volume":"44","author":"Dollberg","year":"1997","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_54","first-page":"181","article-title":"Role of mTOR Complex 1 Signaling Pathway in the Pathogenesis of Diabetes Complications; A Mini Review","volume":"10","author":"Yarahmadi","year":"2021","journal-title":"Int. J. Mol. Cell. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"J\u00f8rgensen, S.H., Emdal, K.B., Pedersen, A.-K., Axelsen, L.N., Kildegaard, H.F., Demozay, D., Pedersen, T.A., Gr\u00f8nborg, M., Slaaby, R., and Nielsen, P.K. (2024). Multi-layered proteomics identifies insulin-induced upregulation of the EphA2 receptor via the ERK pathway which is dependent on low IGF1R level. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-77817-5"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.2337\/db10-0311","article-title":"In utero exposure to maternal diabetes impairs vascular expression of prostacyclin receptor in rat offspring","volume":"59","author":"Perret","year":"2010","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Goto, K., and Kitazono, T. (2019). Endothelium-Dependent Hyperpolarization (EDH) in Diabetes: Mechanistic Insights and Therapeutic Implications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153737"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11507\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:33:27Z","timestamp":1764261207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":57,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311507"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311507","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]}}}