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Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic \u03b2-cell activity and are more insulin resistant. Moreover, dietary Mg2+ supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg2+ regulates glucokinase, KATP channels, and L-type Ca2+ channels in pancreatic \u03b2-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg2+ concentrations, making Mg2+ a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg2+ homeostasis. In the kidney, insulin activates the renal Mg2+ channel transient receptor potential melastatin type 6 that determines the final urinary Mg2+ excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg2+ concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg2+ on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.<\/jats:p>","DOI":"10.2337\/db15-1028","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T17:42:27Z","timestamp":1450806147000},"page":"3-13","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":287,"title":["Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?"],"prefix":"10.2337","volume":"65","author":[{"given":"Lisanne M.M.","family":"Gommers","sequence":"first","affiliation":[{"name":"Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost G.J.","family":"Hoenderop","sequence":"additional","affiliation":[{"name":"Department of Physiology, Radboud Institute 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