Magnesium supplementation improves diabetic mitochondrial and cardiac diastolic function

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

doi:10.1172/jci.insight.123182

Cited by 53 publications

(61 citation statements)

References 45 publications

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“…Magnesium was reported tightly linked to mitochondria physiology. Liu et al found that magnesium may improve mitochondrial function by increasing ATP and decreasing mitochondrial ROS and calcium overload 19 . Ha et al reported the regulation of magnesium on mitochondrial biogenesis via AMPK signals pathway 20 .…”

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confidence: 99%

NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis

Zhao

Zhang

et al. 2020

Sci Rep

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The highly selective magnesium transporter non-imprinted in Prader-Willi/Angelman syndrome region protein 2 (NIPA2) has recently been associated with the development and progression of type 2 diabetes osteoporosis, but the mechanisms involved are still poorly understood. Because mitophagy is involved in the pathology of type 2 diabetes osteoporosis, the present study aimed to explore the relationship among NIPA2, mitophagy and osteoblast osteogenic capacity. NIPA2 expression was reduced in C57BKS background db/db mice and in vitro models of type 2 diabetes osteoporosis, and the activation of mitophagy in primary culture osteoblast-derived from db/db mice and in high glucose-treated human fetal osteoblastic cells (hFOB1.19) was observed. Knockdown, overexpression of NIPA2 and pharmacological inhibition of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) showed that NIPA2 increased osteoblast function, which was likely regulated by PTEN induced kinase 1 (PINK1)/E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy via the PGC-1α/ forkhead box O3a(FoxO3a)/mitochondrial membrane potential (MMP) pathway. Furthermore, the negative effect of mitophagy on osteoblast function was confirmed by pharmacological regulation of mitophagy and knockdown of Parkin. Taken together, these results suggest that NIPA2 positively regulates the osteogenic capacity of osteoblasts via the mitophagy pathway in type 2 diabetes. Plasma measurements. Blood samples were collected from the animals' tail veins. The samples were used for measuring the fasting blood glucose (FBG) levels (Roche blood glucose instrument, Roche, Basel, Switzerland). Radioimmunoassay (3v-diagnostic Bioengineer, Shandong, China) was used for the fasting plasma insulin (FINS) analysis, while ELISA (Rat Estrogen/E ELISA Kit, 3v-diagnostic Bioengineer) was used for the plasma estrogen analysis. The insulin sensitivity index (ISI) was calculated as the -ln(FINS•FPG) 42 . Scientific RepoRtS |(2020) 10:3078 | https://doi.

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confidence: 99%

NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis

Zhao

Zhang

et al. 2020

Sci Rep

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“…A decreased [Mg] i could trigger Mg stores such as mitochondria [ 51 , 81 ] to release Mg through SLC41A3 [ 76 ]. Decreased mitochondrial Mg levels ([Mg] m ) could affect further Mg/MgATP-associated mitochondrial signaling and functions, which may explain the mitochondrial reactive oxygen species (ROS) overproduction and decreased ATP levels observed in Mg deficient mice [ 1 , 82 ].…”

Section: Mg Deficiency Induces Metabolic Derangementsmentioning

confidence: 99%

“…This could be attributed to electrolyte disturbances induced by the excessive activation of the renin-angiotensin-aldosterone system (RAAS) [ 5 , 83 , 84 , 85 ] and by long-term use of medications such as diuretics and digoxin in chronic HF [ 9 , 86 , 87 , 88 ]. Hypomagnesemia may increase the risk of CVD by suppressing mitochondrial function with increased oxidative stress and decreased energy production [ 1 , 50 , 89 , 90 ], modulating cardiac ion channels to cause myocardium electrical remodeling [ 8 , 47 , 56 ], and disturbing Ca homeostasis and cardiac contraction [ 1 , 8 , 49 , 82 , 91 ]. Mg deficiency also induces sustained inflammation [ 35 , 92 , 93 , 94 , 95 ] and interrupts insulin signaling [ 26 , 64 , 96 , 97 ], both of which contribute to the development and progression of CVD.…”

Section: Mg Deficiency Induces Metabolic Derangementsmentioning

confidence: 99%

“…The other is diastolic HF as a result of reduced heart filling in diastole, also known as HF with preserved ejection fraction (HFpEF). Recently, our group has reported that magnesium (Mg) supplementation demonstrates significant protective effects on cardiac diastolic function, providing a new possible therapy for HFpEF [ 1 ]. Therefore, review of the effects of Mg on CVD seems timely.…”

Section: Introductionmentioning

confidence: 99%

“…Hypomagnesemia is commonly observed in HF [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ], DM [ 1 , 11 ], CVD [ 6 , 12 , 13 , 14 ], hypertension [ 15 , 16 ], and stroke [ 17 , 18 ], and the presence of hypomagnesemia in these conditions has been nicely reviewed [ 6 , 7 , 8 , 19 , 20 ]. Dietary Mg intake is inversely correlated with the occurrence of metabolic diseases [ 21 , 22 ], such as DM (type 1, 2 and 3) [ 23 , 24 , 25 , 26 ] and hypertension [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Magnesium, Oxidative Stress, Inflammation, and Cardiovascular Disease

Liu

Dudley

2020

Antioxidants

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Hypomagnesemia is commonly observed in heart failure, diabetes mellitus, hypertension, and cardiovascular diseases. Low serum magnesium (Mg) is a predictor for cardiovascular and all-cause mortality and treating Mg deficiency may help prevent cardiovascular disease. In this review, we discuss the possible mechanisms by which Mg deficiency plays detrimental roles in cardiovascular diseases and review the results of clinical trials of Mg supplementation for heart failure, arrhythmias and other cardiovascular diseases.

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Antioxidant/anti‐inflammatory effect of Mg²⁺ in coronavirus disease 2019 (COVID‐19)

Arancibia-Hernández

Aranda-Rivera

Cruz-Gregorio

et al. 2022

Reviews in Medical Virology

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Severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19), characterised by high levels of inflammation and oxidative stress (OS). Oxidative stress induces oxidative damage to lipids, proteins, and DNA, causing tissue damage. Both inflammation and OS contribute to multi‐organ failure in severe cases. Magnesium (Mg 2+ ) regulates many processes, including antioxidant and anti‐inflammatory responses, as well as the proper functioning of other micronutrients such as vitamin D. In addition, Mg 2+ participates as a second signalling messenger in the activation of T cells. Therefore, Mg 2+ deficiency can cause immunodeficiency, exaggerated acute inflammatory response, decreased antioxidant response, and OS. Supplementation with Mg 2+ has an anti‐inflammatory response by reducing the levels of nuclear factor kappa B (NF‐κB), interleukin (IL) ‐6, and tumor necrosis factor alpha. Furthermore, Mg 2+ supplementation improves mitochondrial function and increases the antioxidant glutathione (GSH) content, reducing OS. Therefore, Mg 2+ supplementation is a potential way to reduce inflammation and OS, strengthening the immune system to manage COVID‐19. This narrative review will address Mg 2+ deficiency associated with a worse disease prognosis, Mg 2+ supplementation as a potent antioxidant and anti‐inflammatory therapy during and after COVID‐19 disease, and suggest that randomised controlled trials are indicated.

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Magnesium supplementation improves diabetic mitochondrial and cardiac diastolic function

Cited by 53 publications

References 45 publications

NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis

NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis

Magnesium, Oxidative Stress, Inflammation, and Cardiovascular Disease

Antioxidant/anti‐inflammatory effect of Mg²⁺ in coronavirus disease 2019 (COVID‐19)

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Magnesium supplementation improves diabetic mitochondrial and cardiac diastolic function

Cited by 53 publications

References 45 publications

NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis

NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis

Magnesium, Oxidative Stress, Inflammation, and Cardiovascular Disease

Antioxidant/anti‐inflammatory effect of Mg2+ in coronavirus disease 2019 (COVID‐19)

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Antioxidant/anti‐inflammatory effect of Mg²⁺ in coronavirus disease 2019 (COVID‐19)