Author: Parker Lance Evans
Publisher:
Published: 2022
Total Pages: 0
ISBN-13:
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Skeletal muscle is a highly adaptable tissue. In response to stimuli such as resistance exercise training or trauma/injury, muscle glucose uptake is stimulated to fuel the energetic and biosynthetic demands of growth, repair, and regeneration processes. Understanding how muscle glucose uptake changes in response to resistance training or acute injury may advance new therapies for patients with type 2 diabetes or those with muscle trauma. Therefore, the overall objective of this dissertation was to determine the transport mechanism(s) used by skeletal muscle to increase glucose uptake in response to mechanical overload, a model of resistance exercise training, as well as in response to acute injury induced by barium chloride injection. AIM 1: Determine if glucose transporter 6 (GLUT6) is necessary for mechanical overload-stimulated skeletal muscle glucose uptake and hypertrophic growth. Mechanical overload stimulates an increase in GLUT6 levels in mouse skeletal muscle. However, its role in overload-stimulated muscle adaptations was unknown. Overload was induced by unilateral synergist muscle ablation surgery in mice lacking GLUT6 in all cells. After 5 days, muscle weight and glucose uptake were assessed. Neither overload-stimulated muscle growth nor glucose uptake were impaired in the mice lacking GLUT6. Lack of impairment in overload-induced glucose uptake and growth demonstrates that GLUT6 does not play an essential role in mediating overload-stimulated glucose uptake or growth in muscle. AIM 2: Determine if chemical damage-induced acute muscle injury stimulates glucose uptake via an adaptation intrinsic to skeletal muscle, and if so to determine the glucose transport mechanism(s) responsible for this effect. Glucose metabolism increases in skeletal muscle acute injured by chemical damage. Whether this is due to an adaptation intrinsic to the muscle tissue versus an in vivo factor(s) such as enhanced blood flow or nerve activity was unknown. Acute muscle injury was induced in mice by intramuscular injection of the chemical barium chloride. In isolated skeletal muscles, barium chloride stimulated glucose uptake was observed at 3-, 5-, 7- and 10-days post injection. This exciting ex-vivo glucose uptake finding demonstrated that chemical damage-induced acute injury stimulates muscle glucose uptake via an adaptation intrinsic to the muscle tissue. Additional key characteristics of the glucose transport mechanism underlying this adaptation included: 1) inhibitable by the facilitative glucose transporter inhibitor, cytochalasin B; 2) not dependent on glucose transporter 1 (GLUT1) expression in muscle cells; 3) not dependent on glucose transporter 1 (GLUT4) expression in muscle cells; and 4) not dependent on glucose transporter 6 (GLUT6) expression in any cell type. The findings presented in this dissertation are significant because they add to the growing body of evidence demonstrating that skeletal muscle tissue can metabolically adapt to stimuli such as chronic muscle overload or acute trauma/injury by stimulating a novel glucose transport mechanism intrinsic to the muscle tissue. Characterization of this transport mechanism(s) represents a key first step in the development of new therapies for individuals suffering from type 2 diabetes or acute muscle trauma/injury.
