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

Peter R. T. Bowman, Godfrey L. Smith, Gwyn W. Gould

Research output: Contribution to journalArticle

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
LanguageEnglish
Article numbere0217885
Number of pages16
JournalPLoS One
Volume14
Issue number7
DOIs
Publication statusPublished - 25 Jul 2019

Fingerprint

Induced Pluripotent Stem Cells
Stem cells
Cardiac Myocytes
Insulin
Glucose
glucose
insulin
Facilitative Glucose Transport Proteins
Bioelectric potentials
Diabetic Cardiomyopathies
Phenotype
uptake mechanisms
phenotype
Medicine
glucose transporters
vascular diseases
Masks
Regenerative Medicine
protein transport
cardiomyopathy

Keywords

  • cardiac medicine
  • cardiac disease
  • regenerative
  • stem cells
  • diabetic cardiomyopathy
  • GLUT4

Cite this

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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",
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GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes. / Bowman, Peter R. T.; Smith, Godfrey L.; Gould, Gwyn W.

In: PLoS One, Vol. 14, No. 7, e0217885, 25.07.2019.

Research output: Contribution to journalArticle

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