title: Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?
abstract: Over the past decades, hypomagnesemia (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). 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 β-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic β-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) 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.
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Lisanne M M
authors.initials: LM
authors.lastname: Gommers
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Joost G J
authors.initials: JG
authors.lastname: Hoenderop
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: René J M
authors.initials: RJ
authors.lastname: Bindels
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, U.K. jeroen.debaaij@radboudumc.nl.
authors.forename: Jeroen H F
authors.initials: JH
authors.lastname: de Baaij
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D019587:Dietary Supplements; D018450:Disease Progression; D005941:Glucokinase / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism* / Q000627:therapeutic use; D008275:Magnesium Deficiency / Q000188:drug therapy / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D049992:Sodium Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy / Q000378:metabolism*; D000098854:Kcnj10 Channel
chemical_list: D001786:Blood Glucose; D020746:Calcium Channels, L-Type; D007328:Insulin; D054086:KATP Channels; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D049992:Sodium Chloride Symporters; D006003:Glycogen; D005941:Glucokinase; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium