Insulin modulation of intracellular free magnesium in heart: involvement of protein kinase C

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Abstract
In the present study of rat heart using 31P‐nuclear magnetic resonance, we examined the interaction between β‐adrenergic and insulin receptors in terms of the intracellular free Mg2+ concentration ([Mg2+]i) regulation. [Mg2+]i was estimated from the separation of the chemical shifts of the α‐ and β‐adenosine triphosphate (ATP) peaks, using the dissociation constant of MgATP 87 μM (established recently). In normal (phosphate‐free Krebs‐Henseleit) solution, [Mg2+]i was approximately 1.02 mM. Insulin at physiological and pathological concentrations increased [Mg2+]i and contractility in a dose‐dependent manner. Insulin (more than 100 μu ml−1) suppressed the decrease in [Mg2+]i caused by isoprenaline (100 nM), and these effects of insulin on [Mg2+]i and contractility were blocked by LY333531 (macrocyclic bis (indolyl) maleimide, 100 nM), a protein kinase C (PKC) inhibitor. The isoprenaline‐induced decrease in the concentrations of ATP ([ATP]) with insulin application was significantly smaller than that without insulin. Insulin modulates [Mg2+]i and haemodynamics, presumably via activation of PKC, thereby antagonizing the reduction of [Mg2+]i induced by β‐adrenoceptor stimulation. British Journal of Pharmacology (2000) 130, 731–738; doi:10.1038/sj.bjp.0703361