CaMKKα stimulates skeletal muscle glucose uptake independent of increases in glucose transporter expression

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Activation of Ca2+/calmodulin‐dependent protein kinase kinase α (CaMKKα) signaling in mouse skeletal muscle stimulates glucose uptake by ~2.5‐fold; yet the mechanism by which CaMKKα increases uptake is unknown. Muscle glucose uptake is increased by altering the expression and/or relocalization of sarcolemmal‐bound glucose transporters. The goal of this study was to determine whether CaMKKα stimulates glucose uptake by increasing the expression of glucose transporters found in muscle (i.e. GLUT1, GLUT4, GLUT8, and GLUT12). Plasmid DNA containing either constitutively active CaMKKα or empty vector were transfected into mouse tibialis anterior muscles by in vivo electroporation. Two weeks later, muscles were collected to assess CaMKKα and glucose transporter mRNA levels. Muscles transfected with active CaMKKα exhibited an 11.5‐fold increase in CaMKKα expression, a level previously shown to stimulate glucose uptake. Surprisingly, in muscles expressing active CaMKKα, there was a significant reduction in GLUT4 (24%) and GLUT12 (35%) expression, with no change in GLUT1 and GLUT8 expression. These results show that active CaMKKα stimulates muscle glucose uptake independent of increased glucose transporter mRNA expression, suggesting that CaMKKα may stimulate glucose uptake via a relocalization of glucose transporters on the sarcolemmal membrane. SUPPORT: NIH R00AR056298, ECU start‐up funds.