PMID- 26696633
OWN - NLM
STAT- MEDLINE
DCOM- 20160428
LR  - 20221109
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 65
IP  - 1
DP  - 2016 Jan
TI  - Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?
PG  - 3-13
LID - 10.2337/db15-1028 [doi]
AB  - 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 beta-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 
      beta-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.
CI  - (c) 2016 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Gommers, Lisanne M M
AU  - Gommers LM
AD  - Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud 
      University Nijmegen Medical Center, Nijmegen, the Netherlands.
FAU - Hoenderop, Joost G J
AU  - Hoenderop JG
AD  - Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud 
      University Nijmegen Medical Center, Nijmegen, the Netherlands.
FAU - Bindels, Rene J M
AU  - Bindels RJ
AD  - Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud 
      University Nijmegen Medical Center, Nijmegen, the Netherlands.
FAU - de Baaij, Jeroen H F
AU  - de Baaij JH
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Insulin)
RN  - 0 (KATP Channels)
RN  - 0 (Kcnj10 (channel))
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Sodium Chloride Symporters)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.1.2 (Glucokinase)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - I38ZP9992A (Magnesium)
SB  - IM
MH  - Blood Glucose/metabolism
MH  - Calcium Channels, L-Type/metabolism
MH  - Diabetes Mellitus, Type 2/complications/*metabolism
MH  - Dietary Supplements
MH  - Disease Progression
MH  - Glucokinase/metabolism
MH  - Glycogen/biosynthesis
MH  - Glycolysis
MH  - Humans
MH  - Inflammation
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/metabolism
MH  - KATP Channels/metabolism
MH  - Liver/metabolism
MH  - Magnesium/*metabolism/therapeutic use
MH  - Magnesium Deficiency/drug therapy/*metabolism
MH  - Obesity/metabolism
MH  - Potassium Channels, Inwardly Rectifying/metabolism
MH  - Sodium Chloride Symporters/metabolism
MH  - Sodium-Potassium-Exchanging ATPase/metabolism
MH  - Water-Electrolyte Imbalance/drug therapy/*metabolism
EDAT- 2015/12/24 06:00
MHDA- 2016/04/29 06:00
CRDT- 2015/12/24 06:00
PHST- 2015/12/24 06:00 [entrez]
PHST- 2015/12/24 06:00 [pubmed]
PHST- 2016/04/29 06:00 [medline]
AID - 65/1/3 [pii]
AID - 10.2337/db15-1028 [doi]
PST - ppublish
SO  - Diabetes. 2016 Jan;65(1):3-13. doi: 10.2337/db15-1028.