Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes

Pentassuglia, L. and Heim, P. and Lebboukh, S. and Morandi, C. and Xu, L. and Brink, M.. (2016) Neuregulin-1β promotes glucose uptake via PI3K/Akt in neonatal rat cardiomyocytes. American Journal of Physiology: Endocrinology and Metabolism, 310 (9). E782-94.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61442/

Downloads: Statistics Overview


Nrg1beta is critically involved in cardiac development and also maintains function of the adult heart. Studies conducted in animal models showed that it improves cardiac performance under a range of pathological conditions, which led to its introduction in clinical trials to treat heart failure. Recent work also implicated Nrg1beta in the regenerative potential of neonatal and adult hearts. The molecular mechanisms whereby Nrg1beta acts in cardiac cells are still poorly understood. In the present study, we analyzed the effects of Nrg1beta on glucose uptake in neonatal rat ventricular myocytes and investigated to what extent mTOR/Akt signaling pathways are implicated. We show that Nrg1beta enhances glucose uptake in cardiomyocytes as efficiently as IGF-I and insulin. Nrg1beta causes phosphorylation of ErbB2 and ErbB4 and rapidly induces the phosphorylation of FAK (Tyr(861)), Akt (Thr(308) and Ser(473)), and its effector AS160 (Thr(642)). Knockdown of ErbB2 or ErbB4 reduces Akt phosphorylation and blocks the glucose uptake. The Akt inhibitor VIII and the PI3K inhibitors LY-294002 and Byl-719 abolish Nrg1beta-induced phosphorylation and glucose uptake. Finally, specific mTORC2 inactivation after knockdown of rictor blocks the Nrg1beta-induced increases in Akt-p-Ser(473) but does not modify AS160-p-Thr(642) or the glucose uptake responses to Nrg1beta. In conclusion, our study demonstrates that Nrg1beta enhances glucose uptake in cardiomyocytes via ErbB2/ErbB4 heterodimers, PI3Kalpha, and Akt. Furthermore, although Nrg1beta activates mTORC2, the resulting Akt-Ser(473) phosphorylation is not essential for glucose uptake induction. These new insights into pathways whereby Nrg1beta regulates glucose uptake in cardiomyocytes may contribute to the understanding of its regenerative capacity and protective function in heart failure.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > CardioBiology (Brink)
UniBasel Contributors:Brink, Marijke
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:20 Jan 2019 19:02
Deposited On:20 Jan 2019 19:02

Repository Staff Only: item control page