GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes

Bowman, P. R.T., Smith, G. L. and Gould, G. W. (2019) GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes. PLoS ONE, 14(7), e0217885. (doi: 10.1371/journal.pone.0217885) (PMID:31920989) (PMCID:PMC6930865)

[img]
Preview
Text
185173.pdf - Published Version
Available under License Creative Commons Attribution.

1MB

Abstract

Induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) have the potential to transform regenerative cardiac medicine and the modelling of cardiac disease. This is of particular importance in the context of diabetic cardiomyopathy where diabetic individuals exhibit reduced cardiac diastolic contractile performance in the absence of vascular disease, significantly contributing towards high cardiovascular morbidity. In this study, the capacity of iPSC-CM to act as a novel cellular model of cardiomyocytes was assessed. The diabetic phenotype is characterised by insulin resistance, therefore there was a specific focus upon metabolic parameters. Despite expressing crucial insulin signalling intermediates and relevant trafficking proteins, it was identified that iPSC-CM do not exhibit insulin-stimulated glucose uptake. iPSC-CM are spontaneously contractile however contraction mediated uptake was not found to mask any insulin response. The fundamental limitation identified in these cells was a critical lack of expression of the insulin sensitive glucose transporter GLUT4. Using comparative immunoblot analysis and the GLUT-selective inhibitor BAY-876 to quantify expression of these transporters, we show that iPSC-CM express high levels of GLUT1 and low levels of GLUT4 compared to primary cardiomyocytes and cultured adipocytes. Interventions to overcome this limitation were unsuccessful. We suggest that the utility of iPSC-CMs to study cardiac metabolic disorders may be limited by their apparent foetal-like phenotype.

Item Type:Articles
Additional Information:GLS and GWG were supported by the British heart Foundation grant ref PG/18/47/33822 (www.bhf.org.uk); and GWG was also supported by Diabetes UK grant 13/0004696 (www.diabetes.org.uk).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gould, Professor Gwyn and Bowman, Mr Peter and Smith, Professor Godfrey
Authors: Bowman, P. R.T., Smith, G. L., and Gould, G. W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2019 Bowman et al.
First Published:First published in PLoS ONE 14(7):e0217885
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
684311BHF 4 Year PhD Studentship AwardRhian TouyzBritish Heart Foundation (BHF)FS/14/61/31284RI CARDIOVASCULAR & MEDICAL SCIENCES
704461How does Cholesterol regulate insulin action in adipocytes?Gwyn GouldDiabetes UK (DIABETUK)15/0005246RI MOLECULAR CELL & SYSTEMS BIOLOGY