Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X

Barbagallo, Mario; Lj, Dominguez; Galioto, Antonio; Ferlisi, Anna; Cani, Calogero; Malfa, Loriano; Pineo, Antonella; Busardo, Adele; Paolisso, Giuseppe

doi:10.1016/s0098-2997(02)00090-0

Cited by 401 publications

(370 citation statements)

References 65 publications

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“…Because Mg 2+ is very important for β-cell function (5) and sensitivity of IRs to insulin (6,12), we speculate that the presence of TRPM6(V 1393 I) and TRPM6(K 1584 E) in these women may lead to a hypomagnesemic state resulting in impaired β-cell function and insulin secretion and/or IR sensitivity. Therefore, these women develop an impaired glucose tolerance with a higher risk for GDM.…”

Section: Discussionmentioning

confidence: 99%

“…There is growing evidence suggesting that Mg 2+ deficiency is a significant risk factor for the development of insulin resistance and subsequently hypertension and DM2 (5)(6)(7)(8), but the underlying molecular mechanism is unknown. The first evidence suggesting a direct connection between Mg 2+ deficiency and the occurrence of metabolic diseases came from the identification of a monogenic disease primarily characterized by significant hypomagnesemia that was caused by a mutation in a mitochondrial tRNA (9).…”

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confidence: 99%

“…It is involved in multiple steps of the insulin signal transduction pathways such as insulin secretion, binding, and receptor activity (5,6,12), suggesting that reduced intracellular Mg 2+ decreases insulin receptor (IR) activity, impairs postreceptor action, and results in an increased insulin resistance. We thus hypothesize that pregnant women who have an altered Mg 2+ handling are particularly prone to severe impairment of glucose tolerance or GDM.…”

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confidence: 99%

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Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy

Nair

Hocher

Verkaart

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

126

137

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Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 (V 1393 I, K 1584 E) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6 (V 1393 I) and TRPM6(K 1584 E), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T 1391 ) and TRPM6(S 1583 ). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6(V 1393 I) and TRPM6(K 1584 E) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6(V 1393 I) and TRPM6(K 1584 E) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6. G estational diabetes mellitus (GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. Babies born to mothers with GDM are typically at increased risk of large for gestational age (LGA), low blood sugar, and jaundice (1). Women with GDM are at a higher risk for preeclampsia and Caesarean section (1) as well as developing diabetes mellitus type 2 (DM2) later in life (2). GDM affects 3-10% of pregnancies, depending on the population studied. No specific cause has been identified, but it is believed that in particular sex hormones (i.e., estrogen, progesterone, prolactin) produced during pregnancy increases a woman's resistance to insulin, resulting in impaired glucose tolerance (1, 3). Moreover, pregnant women are prone to lose magnesium (Mg 2+ ). Bardicef et al. (4) demonstrated that pregnancy itself is a condition of intracellular Mg 2+ depletion. This depletion was more pronounced in women affected by GDM. The elevation in female hormones as well as Mg 2+ deficiency during pregnancy impairs insulin sensitivity and these disturbances may even act synergistically.There is growing evidence suggesting that Mg 2+ deficiency is a significant risk factor for the development of insulin resistance and subsequently hypertension and DM2 (5-8), but the underlying molecular mechanism is unknown. The first evidence suggesting a direct connection between Mg 2+ deficiency and the occurrence of metabolic diseases came from the identification of a monogenic disease primarily characterized by significant hypomagnesemia that was caused by a mutation in a mitochondrial tRNA (9). Moreover, in a recent genome-wide association (GWA) study, it was demonstrated that certain SNPs nominally associated with hypomagnesemia also correlate with fasting glucose levels, again supporting the hypothesis of a direct link between Mg 2+ a...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy

Nair

Hocher

Verkaart

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

126

137

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“…Vermutet wird, dass der niedrige Magnesiumgehalt durch eine verminderte Magnesiumaufnahme oder erhöhte Verluste von Magnesium mit dem Urin zustande kommen (osmotische Diurese) (Barbagallo et al 2003, Ponder et al 1990). Der Magnesiummangel beeinflusst wiederum die Tyrosin-Kinase-Aktivität des Insulinrezeptors und die Signaltransduktion auf Post-RezeptorEbene und kann so eine Insulinresistenz fördern (Barbagallo et al 2003).…”

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Oral supplementation of magnesium aspartate hydrochloride in horses with Equine Metabolic Syndrome

Winter¹,

Liertz²,

Merle³

et al. 2016

PHK

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Diabetes mellitus type 2 is a worldwide problem in human medicine as is the equine equivalent "Equine Metabolic Syndrome" (EMS). In humans, an inverse relationship between serum magnesium content and the incidence of diabetes mellitus type II has been shown. Humans with peripheral insulin resistance often show cellular magnesium deficits and multiple studies have demonstrated the beneficial effect of dietary magnesium supplementation on insulin sensitivity. One study has evaluated the effects of magnesium supplementation on insulin sensitivity in laminitic horses and could not find differences. In this previous study, a different magnesium formulation (magnesium oxide) and dosage had been used. The purpose of this study was to evaluate the effects of an oral supplementation with magnesium aspartate hydrochloride in horses with Equine Metabolic Syndrome. The study was performed on five horses (four mares and one gelding) of different breeds, aged seven to 26 years with Equine Metabolic Syndrome based on the results of a CGIT (Combined Glucose Insulin Tolerance Test). In these horses body weight, Body Condition Score (BCS) and Cresty Neck Score (CNS) were assessed. The following blood parameters were measured in the serum: magnesium (Mg 2+ ), ACTH, fructosamine, reciprocal inverse square of insulin (RISQI) and modified insulin to glucose ratio (MIRG). Gamma-glutamyltransferase (GGT) and triglyzerides (TG) were measured in EDTA blood samples. All horses were supplemented with 30 mg/kg BW magnesium as magnesium aspartate hydrochloride for a time period of three month. Afterwards all blood parameters and the CGIT were repeated. A Wilcoxon signed rank test was used for non-normally distributed data. Statistical significance was set at 95 %. All horses had increased BCS and CNS ). The magnesium content in the serum, ACTH, GGT, TG and MIRG before supplementation were within the reference ranges in all horses. The fructosamine content was increased in horses one, four and five. RISQI was decreased in horse five. During the magnesium supplementation, no adverse effects were observed. There were no significant changes in body weight, BCS and CNS. There were also no significant changes regarding serum magnesium concentration, ACTH, RISQI and MIRG or GGT and TG. There was a tendency for decreased fructosamine concentration, which was also not statistically significant. In three of five horses the CGIT after magnesium supplementation was negative. These horses reached their glucose baseline levels after at least 45 minutes, while insulin (baseline and after 45 minutes) was within the reference ranges. The remaining two horses did not show significant differences compared to the beginning of the trial. It is concluded that the supplementation of magnesium aspartate hydrochloride in horses with Equine Metabolic Syndrome can have positive effects on the insulin sensitivity. Further examinations with more horses are necessary.

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“…It plays a crucial role in glucose metabolism and insulin homeostasis [12,13]. Deficient magnesium intake may be a risk factor for the development of type 2 diabetes [14][15][16] and metabolic syndrome [17,18].…”

Section: Introductionmentioning

confidence: 99%

Obesity, Weight Stigma and Discrimination

Jackson¹

2016

J Obes Eat Disord

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The efficacy of a new dietary mineral product based on natural ingredients was investigated in this comparative randomized control group study. The formulation is based on the middle calcareous layer of oyster shells, in homeopathic and traditional medicine known as calcarea carbonica, as well as iodine, magnesium and chromium. Fourteen none-smoking overweight subjects (BMI ≥ 25.5 kg/m 2 ) were invited to participate in the study. The results show that during a treatment period of 30 days significant reduction are seen both in body weight (BW) and body mass index (BMI). There was also a positive change in waist-and hip circumference, although this change was not statistically significant. Previous studies have shown that all four main ingredients in the formulation might have positive effects on body weight and body composition. This product shows promising results, but additional research is warranted to further clarify the mechanisms responsible for this effect.

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Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X

Cited by 401 publications

References 65 publications

Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy

Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy

Oral supplementation of magnesium aspartate hydrochloride in horses with Equine Metabolic Syndrome

Obesity, Weight Stigma and Discrimination

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