Insulin modulation of intracellular free magnesium in heart: involvement of protein kinase C.
In the present study of rat heart using (31)P-nuclear magnetic resonance, we examined the interaction between beta-adrenergic and insulin receptors in terms of the intracellular free Mg(2+) concentration ([Mg(2+)](i)) regulation. [Mg(2+)](i) was estimated from the separation of the chemical shifts of the alpha- and beta-adenosine triphosphate (ATP) peaks, using the dissociation constant of MgATP 87 microM (established recently). In normal (phosphate-free Krebs-Henseleit) solution, [Mg(2+)](i) was approximately 1.02 mM. Insulin at physiological and pathological concentrations increased [Mg(2+)](i) and contractility in a dose-dependent manner. Insulin (more than 100 micro(u) ml(-1)) suppressed the decrease in [Mg(2+)](i) caused by isoprenaline (100 nM), and these effects of insulin on [Mg(2+)](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 [Mg(2+)](i) and haemodynamics, presumably via activation of PKC, thereby antagonizing the reduction of [Mg(2+)](i) induced by beta-adrenoceptor stimulation.
Amano
T
T
The Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, 466-8550, Japan. tatmat@tsuru.med.nagoya-u.ac.jp
Matsubara
T
T
Watanabe
J
J
Nakayama
S
S
Hotta
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; D007328:Insulin; D008301:Maleimides; D010710:Phosphates; D010725:Phosphocreatine; C099154:ruboxistaurin; D000255:Adenosine Triphosphate; D014700:Verapamil; D011493:Protein Kinase C; D008274:Magnesium; D007545:Isoproterenol