Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells

Recent observations have suggested that creatine supplementation might have a beneficial effect on glucoregulation in skeletal muscle. However, conclusive studies on the direct effects of creatine on glucose uptake and metabolism are lacking. The objective of this study was to investigate the effects of creatine supplementation on basal and insulin-stimulated glucose transporter (GLUT4) translocation, glucose uptake, glycogen content, glycogen synthesis, lactate production, glucose oxidation and AMP-activated protein kinase (AMPK) phosphorylation in L6 rat skeletal muscle cells. Four treatment groups were studied: control, insulin (100 nm), creatine (0.5 mm) and creatine + insulin. After 48 h of creatine supplementation the creatine and phosphocreatine contents of L6 myoblasts increased by similar to9.3- and similar to5.1-fold, respectively, but the ATP content of the cells was not affected. Insulin significantly increased 2-deoxyglucose uptake (similar to 1.9-fold), GLUT4 translocation (similar to 1.8-fold), the incorporation of D- [U-C-14] glucose into glycogen (similar to2.3-fold), lactate production (similar to1.5-fold) and (CO2)-C-14 production (similar to1.5-fold). Creatine neither altered the glycogen and GLUT4 contents of the cells nor the insulin-stimulated rates of 2-DG uptake, GLUT4 translocation, glycogen synthesis and glucose oxidation. However, creatine significantly reduced by similar to42% the basal rate of lactate production and increased by similar to40% the basal rate of (CO2)-C-14 production. This is in agreement with the similar to35% increase in citrate synthase activity and also with the similar to2-fold increase in the phosphorylation of both alpha-1 and alpha-2 isoforms of AMPK after creatine supplementation. We conclude that 48 It of creatine supplementation does not alter insulin-stimulated glucose uptake and glucose metabolism; however, it activates AMPK, shifts basal glucose metabolism towards oxidation and reduces lactate production in L6 rat skeletal muscle cells.