{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:39:21Z","timestamp":1784036361425,"version":"3.55.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003092","name":"Diabetes Fonds","doi-asserted-by":"publisher","award":["2017-81-014"],"award-info":[{"award-number":["2017-81-014"]}],"id":[{"id":"10.13039\/501100003092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Type 2 diabetes (T2D) is characterized by a decreased insulin sensitivity. Magnesium (Mg<jats:sup>2+<\/jats:sup>) deficiency is common in people with T2D. However, the molecular consequences of low Mg<jats:sup>2+<\/jats:sup> levels on insulin sensitivity and glucose handling have not been determined in adipocytes. The aim of this study is to determine the role of Mg<jats:sup>2+<\/jats:sup> in the insulin-dependent glucose uptake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, the association of low plasma Mg<jats:sup>2+<\/jats:sup> with markers of insulin resistance was assessed in a cohort of 395 people with T2D. Secondly, the molecular role of Mg<jats:sup>2+<\/jats:sup> in insulin-dependent glucose uptake was studied by incubating 3T3-L1 adipocytes with 0 or 1 mmol\/L Mg<jats:sup>2+<\/jats:sup> for 24 hours followed by insulin stimulation. Radioactive-glucose labelling, enzymatic assays, immunocytochemistry and live microscopy imaging were used to analyze the insulin receptor phosphoinositide 3-kinases\/Akt pathway. Energy metabolism was assessed by the Seahorse Extracellular Flux Analyzer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In people with T2D, plasma Mg<jats:sup>2+<\/jats:sup> concentration was inversely associated with markers of insulin resistance; i.e., the lower Mg<jats:sup>2+<\/jats:sup>, the more insulin resistant. In Mg<jats:sup>2+<\/jats:sup>-deficient adipocytes, insulin-dependent glucose uptake was decreased by approximately 50% compared to control Mg<jats:sup>2+<\/jats:sup>condition. Insulin receptor phosphorylation Tyr1150\/1151 and PIP3 mass were not decreased in Mg<jats:sup>2+<\/jats:sup>-deficient adipocytes. Live imaging microscopy of adipocytes transduced with an Akt sensor (FoxO1-Clover) demonstrated that FoxO1 translocation from the nucleus to the cytosol was reduced, indicting less Akt activation in Mg<jats:sup>2+<\/jats:sup>-deficient adipocytes. Immunocytochemistry using a Lectin membrane marker and at the membrane located Myc epitope-tagged glucose transporter 4 (GLUT4) demonstrated that GLUT4 translocation was diminished in insulin-stimulated Mg<jats:sup>2+<\/jats:sup>-deficient adipocytes compared to control conditions. Energy metabolism in Mg<jats:sup>2+<\/jats:sup> deficient adipocytes was characterized by decreased glycolysis, upon insulin stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mg<jats:sup>2+<\/jats:sup> increases insulin-dependent glucose uptake in adipocytes and suggests that Mg<jats:sup>2+<\/jats:sup> deficiency may contribute to insulin resistance in people with T2D.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.986616","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T11:30:31Z","timestamp":1661427031000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Magnesium increases insulin-dependent glucose uptake in adipocytes"],"prefix":"10.3389","volume":"13","author":[{"given":"Lynette J.","family":"Oost","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steef","family":"Kurstjens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost G. 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