Functional overload-induced muscle hypertrophy and glucose uptake occurs independent of glucose transporter 4 (GLUT4)

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Shawna McMillin (Creator)
Denise Schmidt McMillin (Creator)
Barbara Khan McMillin (Creator)
Carol Witczak McMillin (Creator)
East Carolina University (ECU )
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Abstract: Functional overload induces a number of adaptations in skeletal muscle that are similar to resistance exercise training , including muscle hypertrophy and glucose uptake. While numerous studies have investigated the molecular/cellular mechanisms underlying overload-induced muscle growth , little is known regarding the mechanism(s) underlying overload-induced glucose uptake. Glucose transporter 4 (GLUT4) is the predominant glucose transporter in muscle; yet surprisingly its role in overload-induced glucose uptake is currently unknown. The goal of this study was to determine whether GLUT4 regulates overload-induced muscle glucose uptake. Overload was induced in mouse plantaris muscle via unilateral synergist ablation of the distal two-thirds of the gastrocnemius and soleus. Muscle weights and ex vivo [3H]-2-deoxy-D-glucose uptake were assessed 5-days later. Overload-induced muscle glucose uptake and growth were not impaired in muscle-specific GLUT4 knockout mice , demonstrating that GLUT4 is not necessary for these processes. To determine which transporter mediates overload-induced glucose uptake , uptake was assessed +/- the sodium-dependent glucose co-transporter (SGLT) inhibitor , phloridzin , or the GLUT inhibitor , cytochalasin B. Cytochalasin B , but not phloridzin , prevented overload-induced glucose uptake demonstrating that GLUT(s) mediate this effect. To narrow down which GLUT , hexose competition experiments were performed. Based on the GLUT's distinct affinities for different hexoses , [3H]-2-deoxy-D-glucose uptake was evaluated against L-glucose , D-glucose , D-fructose , D-galactose , or D-xylose. Overload-induced [3H]-2-deoxy-D-glucose uptake was not inhibited by D-fructose , demonstrating that the fructose-transporting GLUT2 , GLUT5 , GLUT8 , and GLUT12 , do not mediate this effect. In contrast , overload-induced [3H]-2-deoxy-D-glucose uptake was partially impaired by D-galactose and D-xylose , suggesting a role for GLUT1 , GLUT3 , GLUT6 and/or GLUT10. Consistent with this finding , immunoblot analyses demonstrated a 2- to 5-fold increase in GLUT1 , GLUT3 , GLUT6 and GLUT10 protein levels in overload muscles. Collectively , these results demonstrate that GLUT4 is not necessary for overload-induced muscle glucose uptake or growth , and suggest that GLUT1 , GLUT3 , GLUT6 and/or GLUT10 mediate overload-induced glucose uptake.

Additional Information

Language: English
Date: 2017
GLUT, Muscle, functional overload

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