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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.

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  • Authors+Show Affiliations

    ,

    Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

    ,

    Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

    ,

    Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

    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.

    Source

    Diabetes 65:1 2016 Jan pg 3-13

    MeSH

    Blood Glucose
    Calcium Channels, L-Type
    Diabetes Mellitus, Type 2
    Dietary Supplements
    Disease Progression
    Glucokinase
    Glycogen
    Glycolysis
    Humans
    Inflammation
    Insulin
    Insulin Resistance
    Insulin Secretion
    Insulin-Secreting Cells
    KATP Channels
    Liver
    Magnesium
    Magnesium Deficiency
    Obesity
    Potassium Channels, Inwardly Rectifying
    Sodium Chloride Symporters
    Sodium-Potassium-Exchanging ATPase
    Water-Electrolyte Imbalance

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    26696633

    Citation

    Gommers, Lisanne M M., et al. "Hypomagnesemia in Type 2 Diabetes: a Vicious Circle?" Diabetes, vol. 65, no. 1, 2016, pp. 3-13.
    Gommers LM, Hoenderop JG, Bindels RJ, et al. Hypomagnesemia in Type 2 Diabetes: A Vicious Circle? Diabetes. 2016;65(1):3-13.
    Gommers, L. M., Hoenderop, J. G., Bindels, R. J., & de Baaij, J. H. (2016). Hypomagnesemia in Type 2 Diabetes: A Vicious Circle? Diabetes, 65(1), pp. 3-13. doi:10.2337/db15-1028.
    Gommers LM, et al. Hypomagnesemia in Type 2 Diabetes: a Vicious Circle. Diabetes. 2016;65(1):3-13. PubMed PMID: 26696633.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Hypomagnesemia in Type 2 Diabetes: A Vicious Circle? AU - Gommers,Lisanne M M, AU - Hoenderop,Joost G J, AU - Bindels,René J M, AU - de Baaij,Jeroen H F, PY - 2015/12/24/entrez PY - 2015/12/24/pubmed PY - 2016/4/29/medline SP - 3 EP - 13 JF - Diabetes JO - Diabetes VL - 65 IS - 1 N2 - 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. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/26696633/full_citation L2 - http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=26696633 DB - PRIME DP - Unbound Medicine ER -