Tags

Type your tag names separated by a space and hit enter

Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?
Diabetes 2016; 65(1):3-13D

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+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.

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 -