Calcium/Calmodulin‐Activated Protein Kinase may be Important for Regulating GLUT4 Expression in Response to Exercise Training

Abstract

Glucose transporter 4 (GLUT4) expression is increased by muscle activity. Muscle contraction causes myocellular calcium concentration to increase. Elevated cytoplasmic calcium causes activation of the calcium/calmodulin-activated protein kinase (CaMK). In L6 myotubes, CaMK was shown to be responsible for increased GLUT4 expression in response to elevated cytoplasmic calcium. Since calcium and CaMK may be involved in the regulation of GLUT4 in muscle, we have used wild-type (WT) mice and mice expressing a constitutively-active CaMK IV (CaMK-TG) to investigate the role of CaMK in regulation of muscle GLUT4 expression. GLUT4 mRNA was measured in plantaris muscles of WT and CaMK-TG mice by RT-PCR. GLUT4 mRNA was 45% higher (p=0.02) in muscle from CAMK-TG mice than in muscle from WT mice. To investigate the effects of CaMK on GLUT4 expression in response to muscle activity, we measured GLUT4 mRNA in plantaris muscle from WT and CaMK-TG mice trained in a running wheel for 14 days. Exercise training caused GLUT4 mRNA to increase significantly (53%, p=.005) in WT mice. However, exercise training did not increase the level of GLUT4 mRNA in CaMK-TG mice. Because CaMK activity is sufficient to cause increased GLUT4 expression and because exercise training does not induce further increases in GLUT4 content, we believe that CaMK may be an important factor causing the typical increase in GLUT4 in response to exercise.