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

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

Excitation and decay of projectile-like fragments formed in dissipative peripheral collisions at intermediate energies

Projectile-like fragments (PLF:15<=Z<=46) formed in peripheral and mid-peripheral collisions of 114Cd projectiles with 92Mo nuclei at E/A=50 MeV have been detected at very forward angles, 2.1 deg.<=theta_lab<=4.2 deg. Calorimetric analysis of the charged particles observed in coincidence with the PLF reveals that the excitation of the primary PLF is strongly related to its velocity damping. Furthermore, for a given V_PLF*, its excitation is not related to its size, Z_PLF*. For the largest velocity damping, the excitation energy attained is large, approximately commensurate with a system at the limiting temperatureComment: 5 pages, 6 figure