Insulin and contraction are the most important regulators of glucose utilization in cardiac muscle. In contrast with insulin, the intracellular signalling elements of contraction have remained unexplored. In the present studies, adult rat ventricular cardiomyocytes were electrically stimulated to perform rhythmic contractions to permit the determination of potential sites of convergence of contraction and insulin signalling to glucose transport. The participation of phosphoinositide 3-kinase (PI-3K) in Ca2+- and contraction-stimulated 3-O-methylglucose transport was suggested by the great sensitivity of this process towards the PI-3K inhibitors wortmannin and LY294002 and by the presence of PI-3K activity in anti-phosphotyrosine immunoprecipitates from contracted cells. Initial signalling events of insulin action, including receptor kinase activation, the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 and the recruitment of PI-3K to IRS-1 and IRS-2, were found not to be involved in contraction-mediated signalling. However, immunoprecipitation of p85α revealed a markedly enhanced tyrosine phosphorylation of an unknown co-precipitated 200 kDa protein in response to both stimuli. It is concluded that contraction-regulated cardiac glucose transport involves the activation of PI-3K in response to upstream signalling pathways different from that of insulin.
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Research Article|
March 07 2000
Molecular mechanisms of contraction-regulated cardiac glucose transport
Martin TILL;
Martin TILL
1Laboratory of Molecular Cardiology, Diabetes Research Institute, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany
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D. Margriet OUWENS;
D. Margriet OUWENS
1Laboratory of Molecular Cardiology, Diabetes Research Institute, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany
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Alexandra KESSLER;
Alexandra KESSLER
1Laboratory of Molecular Cardiology, Diabetes Research Institute, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany
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Jürgen ECKEL
Jürgen ECKEL
1
1To whom correspondence should be addressed (e-mail eckel@;uni-duesseldorf.de).
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Publisher: Portland Press Ltd
Received:
September 20 1999
Revision Received:
November 15 1999
Accepted:
January 04 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 346 (3): 841–847.
Article history
Received:
September 20 1999
Revision Received:
November 15 1999
Accepted:
January 04 2000
Citation
Martin TILL, D. Margriet OUWENS, Alexandra KESSLER, Jürgen ECKEL; Molecular mechanisms of contraction-regulated cardiac glucose transport. Biochem J 15 March 2000; 346 (3): 841–847. doi: https://doi.org/10.1042/bj3460841
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