Assessment of magnesium concentrations by <sup>31</sup>P NMR <i>in vivo</i>

Halvorson, Herbert R.; Linde, A. M. Q. Vande; Helpern, Joseph A.; Welch, K. M. A.

doi:10.1002/nbm.1940050202

Cited by 54 publications

(38 citation statements)

References 12 publications

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“…No significant differences between the groups were observed for the mean basal muscle concentrations of G6P, ADP, phosphocreatine (PCr), intracellular phosphate (Pi), and intracellular pH, which are summarized in Table 1 (20).…”

Section: Resultsmentioning

confidence: 98%

Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus.

Rothman

Magnusson²,

Cline³

et al. 1995

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

303

203

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Recent studies have demonstrated that reduced insulin-stimulated muscle glycogen synthesis is the major cause of insulin resistance in patients with non-insulindependent diabetes mellitus (NIDDM). This reduced rate has been assigned to a defect in either glucose transport or hexokinase activity. However it is unknown whether this is a primary or acquired defect in the pathogenesis of NIDDM. To examine this question, we measured the rate of muscle glycogen synthesis and the muscle glucose 6-phosphate (G6P) concentration using 13C and 31P NMR spectroscopy as well as oxidative and nonoxidative glucose metabolism in six lean, normoglycemic offspring of parents with NIDDM and seven age/weight-matched control subjects under hyperglycemic ("11 mM)-hyperinsulinemic (-480 pM) clamp conditions.The offspring of parents with NIDDM had a 50% reduction in total glucose metabolism, primarily due to a decrease in the nonoxidative component. The rate of muscle glycogen synthesis was reduced by 70%o (P < 0.005) and muscle G6P concentration was reduced by 40% (P < 0.003), which suggests impaired muscle glucose transport/hexokinase activity.These changes were similar to those previously observed in subjects with fully developed NIDDM. When the control subjects were studied at similar insulin levels (-440 pM) but euglycemic plasma glucose concentration (-5 mM), both the rate of glycogen synthesis and the G6P concentration were reduced to values similar to the offspring of parents with NIDDM. We conclude that insulin-resistant offspring of parents with NIDDM have reduced nonoxidative glucose metabolism and muscle glycogen synthesis secondary to a defect in muscle glucose transport/hexokinase activity prior to the onset of overt hyperglycemia. The presence of this defect in these subjects suggests that it may be the primary factor in the pathogenesis of NIDDM.Insulin resistance is a primary factor responsible for glucose intolerance in type II, or non-insulin-dependent diabetes mellitus (NIDDM). Studies on both families and populations with a high incidence of NIDDM have found that reduced insulindependent glucose metabolism is frequently found in nondiabetic relatives (1-4) and that it is the best predictor for the later development of the disease (1, 4). Using 13C NMR, we have shown that muscle glycogen synthesis accounts for the majority of insulin-dependent glucose metabolism under hyperglycemic-hyperinsulinemic conditions in healthy control subjects and that reduced muscle glycogen synthesis is the major factor responsible for impaired glucose metabolism in subjects with NIDDM (5). Glucose 6-phosphate (G6P) is an intermediate in the muscle glycogen synthesis pathway, and its concentration depends on the relative activities of the muscle glycogen synthase enzyme and glucose transport into muscle (6-9). In a recent study using 31P NMR, we (6) found that muscle G6P concentration was reduced in subjects with NIDDM, suggesting that reduced activity of muscle glucose transporters or of hexokinase is responsible for the impai...

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Section: Resultsmentioning

confidence: 98%

Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus.

Rothman

Magnusson²,

Cline³

et al. 1995

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

303

203

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“…Most previous NMR studies of human brain pH and [Mg 2ϩ ] have used either single-voxel localization techniques (4,16) or measurements of selected regions of interest from spectroscopic imaging data sets (10). However, it is possible to create images of both pH and [Mg 2ϩ ] by using spectroscopic imaging, which permits the mapping of regional variations of these quantities.…”

Section: Intracellular Free Magnesium Concentrations ([Mgmentioning

confidence: 99%

“…]) and pH can be calculated from in vivo 31 phosphorus ( 31 P) nuclear magnetic resonance (NMR) chemical-shift measurements (1)(2)(3)(4)(5)(6). The former is derived most often from the chemical shift difference between the ␣ and ␤ resonances of adenosine triphosphate (ATP), whereas the latter usually is calculated from the chemical shift of inorganic phosphate (P i ) (5,6).…”

Section: Intracellular Free Magnesium Concentrations ([Mgmentioning

confidence: 99%

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Magnesium and pH imaging of the human brain at 3.0 Tesla

et al. 1999

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“…Flow-rephased gradient echo proton images were then acquired to control the position and to determine the volume of interest. Subsequent nonlocalized shimming was also performed on protons leading to water linewidths between 8 and 11 Hz within less than 5 min.…”

Section: Nm R Spectroscopic Investigationsmentioning

confidence: 99%

Phosphorus J‐coupling constants of ATP in human brain

Jung

Staubert

Widmaier

et al. 1997

Magnetic Resonance in Med

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Proton decoupled 31P NMR spectroscopy of the occipital brain of healthy volunteers was performed with a 1.5 T whole-body imager. By use of two-dimensional chemical-shift imaging in combination with slice-selective excitation well resolved localized spectra (38 ml) were obtained within 34 min from which the homonuclear 31P-31P J-coupling constants of ATP could be determined: J(gammabeta) = 16.1 Hz +/- 0.2 Hz and J(alphabeta) = 16.3 Hz +/- 0.1 Hz (mean +/- SEM, n = 14). Both, the J-coupling constants and the chemical-shift difference between alpha- and beta-ATP (delta(alphabeta) = 8.61 ppm +/- 0.01 ppm) were used to calculate the concentration of intracellular free magnesium. The concentrations are 0.39 mM +/- 0.09 mM by using the average of both coupling constants of each spectrum, which is in fair agreement with 0.32 mM +/- 0.01 mM obtained from the chemical shift of alpha and beta phosphate resonances, which is the more accurate result.

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Assessment of magnesium concentrations by ³¹P NMR in vivo

Cited by 54 publications

References 12 publications

Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus.

Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus.

Magnesium and pH imaging of the human brain at 3.0 Tesla

Phosphorus J‐coupling constants of ATP in human brain

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Assessment of magnesium concentrations by 31P NMR in vivo

Cited by 54 publications

References 12 publications

Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus.

Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus.

Magnesium and pH imaging of the human brain at 3.0 Tesla

Phosphorus J‐coupling constants of ATP in human brain

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Product

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Assessment of magnesium concentrations by ³¹P NMR in vivo