Glucose Transporter 4 (GLUT4) is Not the Only GLUT Responsible for Ca 2+ /Calmodulin‐Dependent Protein Kinase Kinase α (CaMKKα)‐Induced Glucose Uptake in Mouse Skeletal Muscle

Abstract

Chronic activation of Ca2+/calmodulin-dependent protein kinase kinase α (CaMKKα) signaling for 2 weeks stimulates skeletal muscle glucose uptake in both insulin-sensitive and insulin-resistant mice; yet surprisingly the glucose transporter(s) that mediate this effect are currently unknown. The goal of this study was to determine if glucose transporter 4 (GLUT4) is the main glucose transporter responsible for CaMKKα-induced muscle glucose uptake. To stimulate CaMKKα signaling, muscles from 13-14 week old, male, wild-type/control, muscle-specific GLUT4 heterozygous and muscle-specific GLUT4 knockout mice were transfected with plasmid DNA containing constitutively active CaMKKα or empty vector by in vivo electroporation. After 2 weeks, active CaMKKα protein levels were robustly increased and were not different between groups. In vivo muscle [3H]-2-deoxyglucose uptake was examined in the absence of insulin stimulation. Constitutively active CaMKKα increased glucose uptake ~250% in wild-type/control mice, ~100...