Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes.
Cell Commun Signal
; 12: 68, 2014 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-25376904
ABSTRACT
BACKGROUND:
Cardiac hypertrophy is characterized by alterations in both cardiac bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by cardiomyocytes and its use as a substrate for glycolysis and mitochondrial oxidation in order to maintain the high cardiac energy demands. Insulin stimulates Ca(2+) release from the endoplasmic reticulum, however, how this translates to changes in mitochondrial metabolism in either healthy or hypertrophic cardiomyocytes is not fully understood.RESULTS:
In the present study we investigated insulin-dependent mitochondrial Ca(2+) signaling in normal and norepinephrine or insulin like growth factor-1-induced hypertrophic cardiomyocytes. Using mitochondrion-selective Ca(2+)-fluorescent probes we showed that insulin increases mitochondrial Ca(2+) levels. This signal was inhibited by the pharmacological blockade of either the inositol 1,4,5-triphosphate receptor or the mitochondrial Ca(2+) uniporter, as well as by siRNA-dependent mitochondrial Ca(2+) uniporter knockdown. Norepinephrine-stimulated cardiomyocytes showed a significant decrease in endoplasmic reticulum-mitochondrial contacts compared to either control or insulin like growth factor-1-stimulated cells. This resulted in a reduction in mitochondrial Ca(2+) uptake, Akt activation, glucose uptake and oxygen consumption in response to insulin. Blocking mitochondrial Ca(2+) uptake was sufficient to mimic the effect of norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling.CONCLUSIONS:
Mitochondrial Ca(2+) uptake is a key event in insulin signaling and metabolism in cardiomyocytes.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Cardiomegalia
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Miócitos Cardíacos
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Insulina
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Mitocôndrias Cardíacas
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article