{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:38:29Z","timestamp":1760060309836,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Quatar Foundation","award":["QB14 (PJT)","466-851710"],"award-info":[{"award-number":["QB14 (PJT)","466-851710"]}]},{"DOI":"10.13039\/501100007051","name":"Foundation of Health Care Research, Uppsala University","doi-asserted-by":"publisher","award":["QB14 (PJT)","466-851710"],"award-info":[{"award-number":["QB14 (PJT)","466-851710"]}],"id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Family Ernfors Fund","award":["QB14 (PJT)","466-851710"],"award-info":[{"award-number":["QB14 (PJT)","466-851710"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hyperglycemia in early-stage embryogenesis is linked to diabetic embryopathy. High-glucose-concentration-induced accumulation of hexokinase-2 (HK2) may initiate metabolic dysfunction that contributes to diabetic embryopathy, including increased formation of methylglyoxal (MG). In this study, we evaluated changes in HK2 protein levels and embryo dysmorphogenesis in an experimental model of diabetic embryopathy. Rat embryos were cultured with high glucose concentrations, and the effects of glyoxalase 1 (Glo1) inducer, trans-resveratrol and hesperetin (tRES + HESP) were evaluated. Rat embryos, on gestational day 9, were cultured for 48 h in low and high glucose concentrations with or without tRES + HESP. Embryo crown\u2013rump length, somite number, malformation score, concentrations of HK2 and Glo1 protein, rates of glucose consumption, and MG formation were assessed. Under low-glucose conditions, embryos exhibited normal morphogenesis. In contrast, high-glucose conditions led to reduced crown\u2013rump length and somite number, and an increased malformation score. The addition of 10 \u03bcM tRES + HESP reversed these high glucose-induced changes by 60%, 49%, and 47%, respectively. Embryos cultured in high glucose showed increases in HK2 concentration (42%), glucose consumption (75%), and MG formation (27%), normalized to embryo volume. These elevated HK2 levels were normalized by treatment with 10 \u03bcM tRES + HESP. Thus, high-glucose-induced metabolic dysfunction and embryopathy may both be initiated by HK2 accumulation and may be preventable with tRES + HESP treatment.<\/jats:p>","DOI":"10.3390\/antiox14081022","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:02:44Z","timestamp":1755763364000},"page":"1022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Overload of Glucose Metabolism as Initiating Factor in Diabetic Embryopathy and Prevention by Glyoxalase 1 Inducer Dietary Supplement"],"prefix":"10.3390","volume":"14","author":[{"given":"Parri","family":"Wentzel","sequence":"first","affiliation":[{"name":"Department of Medical Cell Biology, Biomedical Center, Uppsala University, 75123 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9184-2980","authenticated-orcid":false,"given":"Mingzhan","family":"Xue","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naila","family":"Rabbani","sequence":"additional","affiliation":[{"name":"QU (Qatar University) Health, Qatar University, University Street, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf J.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology, Biomedical Center, Uppsala University, 75123 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7659-443X","authenticated-orcid":false,"given":"Paul J.","family":"Thornalley","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jsgi.2005.09.007","article-title":"Advances in Understanding the Molecular Causes of Diabetes-Induced Birth Defects","volume":"13","author":"Loeken","year":"2006","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_2","first-page":"73","article-title":"Rate and type of congenital anomalies among offspring of diabetic women","volume":"7","author":"Kucera","year":"1971","journal-title":"J. Reprod. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"237.e1","DOI":"10.1016\/j.ajog.2008.06.028","article-title":"Diabetes mellitus and birth defects","volume":"199","author":"Correa","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Evers, I.M., de Valk, H.W., and Visser, G.H. (2004). 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