Dual effect of the heart-targeting cytokine cardiotrophin-1 on glucose transport in cardiomyocytes

► In cardiomyocytes low concentrations of CT-1 impair stimulation of glucose uptake. ► Low CT-1 activates STAT5, increases SOCS3 and reduces GLUT4. ► STAT5 inhibition restores glucose uptake, insulin signaling and GLUT4 expression. ► High concentrations of CT-1 increase basal and stimulated glucose uptake. ► High CT-1 activates AMPK in a CaMKII-dependent manner.