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Cardiovascular Research Advance Access originally published online on April 5, 2008
Cardiovascular Research 2008 79(2):238-248; doi:10.1093/cvr/cvn093
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Insulin signalling in the heart

Luc Bertrand1,*, Sandrine Horman1,2, Christophe Beauloye1 and Jean-Louis Vanoverschelde1

1 CARD Unit, Division of Cardiology, Université catholique de Louvain, 55, Avenue Hippocrate, CARD5550, 1200 Brussels, Belgium
2 Hormone and Metabolic Research Unit, de Duve Institute, Université catholique de Louvain, Brussels, Belgium

* Corresponding author. Tel: +32 2 764 55 52; fax: +32 2 764 55 36. E-mail address: luc.bertrand{at}uclouvain.be

The main role of insulin in the heart under physiological conditions is obviously the regulation of substrate utilization. Indeed, insulin promotes glucose uptake and its utilization via glycolysis. In addition, insulin participates in the regulation of long-chain fatty acid uptake, protein synthesis, and vascular tonicity. Significant advancements have been made over the last 20 years in the understanding of the signal transduction elements involved in these insulin effects. Among these molecular mechanisms, the phosphatidylinositol 3-kinase/protein kinase B (Akt) pathway is thought to play a crucial role. Under pathological conditions, such as type-2 diabetes, myocardial ischaemia, and cardiac hypertrophy, insulin signal transduction pathways and action are clearly modified. These molecular signalling alterations are often linked to atypical crosstalks with other signal transduction pathways. On the other hand, pharmacological modifications of parallel and interdependent signalling components, such as the AMP-activated protein kinase pathway, are now considered to be a good therapeutic approach to treat insulin-signalling defects such as insulin resistance and type-2 diabetes. In this review, we will focus on the description of the molecular signalling elements involved in insulin action in the heart and vasculature under these different physiological, pathological, and therapeutical conditions.

KEYWORDS Energy metabolism; PKB/Akt; Ischaemia; Protein synthesis; Insulin resistance; AMPK

Time for primary review: 21 days


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