Magnesium supplementation improves diabetic mitochondrial and cardiac diastolic function
Man Liu, … , Anyu Zhou, Samuel C. Dudley Jr.
Man Liu, … , Anyu Zhou, Samuel C. Dudley Jr.
Published January 10, 2019
Citation Information: JCI Insight. 2019;4(1):e123182. https://doi.org/10.1172/jci.insight.123182.
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Research Article Cardiology

Magnesium supplementation improves diabetic mitochondrial and cardiac diastolic function

Abstract

In heart failure and type 2 diabetes mellitus (DM), the majority of patients have hypomagnesemia, and magnesium (Mg) supplementation has improved cardiac function and insulin resistance. Recently, we have shown that DM can cause cardiac diastolic dysfunction (DD). Therefore, we hypothesized that Mg supplementation would improve diastolic function in DM. High-fat diet–induced diabetic mouse hearts showed increased cardiac DD and hypertrophy. Mice with DM showed a significantly increased E/e’ ratio (the ratio of transmitral Doppler early filling velocity [E] to tissue Doppler early diastolic mitral annular velocity [e’]) in the echocardiogram, left ventricular end diastolic volume (LVEDV), incidence of DD, left ventricular posterior wall thickness in diastole (PWTd), and ratio of heart weight to tibia length (HW/TL) when compared with controls. DM mice also had hypomagnesemia. Ventricular cardiomyocytes isolated from DM mice exhibited decreased mitochondrial ATP production, a 1.7- ± 0.2-fold increase of mitochondrial ROS, depolarization of the mitochondrial membrane potential, and mitochondrial Ca2+ overload. Dietary Mg administration (50 mg/ml in the drinking water) for 6 weeks increased plasma Mg concentration and improved cardiac function. At the cellular level, Mg improved mitochondrial function with increased ATP, decreased mitochondrial ROS and Ca2+ overload, and repolarized mitochondrial membrane potential. In conclusion, Mg supplementation improved mitochondrial function, reduced oxidative stress, and prevented DD in DM.

Authors

Man Liu, Euy-Myoung Jeong, Hong Liu, An Xie, Eui Young So, Guangbin Shi, Go Eun Jeong, Anyu Zhou, Samuel C. Dudley Jr.

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Figure 5

Dietary Mg suppressed mitochondrial oxidative stress and repolarized mitochondrial membrane potential in DM mice.

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Dietary Mg suppressed mitochondrial oxidative stress and repolarized mit...
(A) Mitochondrial ATP reduction in DM mice was improved by dietary Mg. Four animals were tested for each group. (B) Elevation of the peak mitochondrial Ca2+ transient in DM mice was reduced by dietary Mg. Cardiomyocytes isolated from the left ventricle of 5–8 animals were tested for each group. (C) Overproduction of mitochondrial superoxide in DM mice was suppressed by dietary Mg. Cardiomyocytes isolated from the left ventricle of 5–7 animals were tested for each group. (D) Mitochondrial membrane potentials measured with JC-1 staining of ratios of red (595 nm) to green (530 nm) fluorescence were depolarized in DM mice and repolarized by dietary Mg. Cardiomyocytes isolated from the left ventricle of 6–7 animals were tested for each group. One-way ANOVA with Bonferroni post hoc test was used; *P < 0.01 vs. control and #P < 0.05 vs. DM. CT, control mice; DM, mice fed with high-fat diet; DM+Mg, mice fed with high-fat diet and Mg in drinking water. mitoCa2+, mitochondrial Ca2+; ΔMFIF–F0, The Δmean of the fluorescence intensity obtained from the subtraction of background fluorescence (F–F0); mitoΔψm, mitochondrial membrane potential.