Conditioning-induced expression of novel glucose transporters in canine skeletal muscle homogenate

Abstract

Athletic conditioning can increase the capacity for insulin-stimulated skeletal muscle glucose uptake through increased sarcolemmal expression of GLUT4 and potentially additional novel glucose transporters. We used a canine model that has previously demonstrated conditioning-induced increases in basal, insulin- and contraction-stimulated glucose uptake to identify whether expression of glucose transporters other than GLUT4 was upregulated by athletic conditioning. Skeletal muscle biopsies were obtained from 12 adult Alaskan Husky racing sled dogs before and after a full season of conditioning and racing, and homogenates from those biopsies were assayed for expression of GLUT1, GLUT3, GLUT4, GLUT6, GLUT8, and GLUT12 using western blots. Athletic conditioning resulted in a 1.31 ± 0.70 fold increase in GLUT1 (p <0.0001), 1.80 ± 1.99 fold increase in GLUT4 (p = 0.005), and 2.46 ± 2.39 fold increase in GLUT12 (p = 0.002). The increased expression of GLUT1 helps explain the previous findings of conditioning-induced increases in basal glucose clearance in this model, and the increase in GLUT12 provides an alternative mechanism for insulin- and contraction-mediated glucose uptake and likely contributes to the substantial conditioning-induced increases in insulin sensitivity in highly trained athletic dogs. Furthermore, these results suggest that athletic dogs can serve as a valuable resource for the study of alternative glucose transport mechanisms in higher mammals.

Dynamics of training and acute exercise-induced shifts in muscular glucose transporter (GLUT) 4, 8, and 12 expression in locomotion versus posture muscles in healthy horses

“…To the best of the authors' knowledge, this is the first study to examine the effect of acute exercise and 8 weeks of harness training on total GLUT4, 8 and GLUT12 protein expression in the m. vastus lateralis and the m. pectoralis of horses. The results related to both GLUT8 and GLUT12 align with results found in the m. vastus lateralis of humans and the m. biceps femoris of dogs (Seki et al, 2006;Barrett and Scott Davis, 2023), suggesting that GLUT8 does not play an essential role in skeletal muscle metabolism during exercise and training. A study by Seki et al (2006) examined the differences in GLUT8 and GLUT12 mRNA expression in the m. vastus lateralis from fifteen untrained and sixteen trained human subjects at rest.…”

“…Similarly, Jose-Cunilleras et al (2005) reported an increase in GLUT4 mRNA transcripts in the m. gluteus medius of seven horses 4 h post exercise following 3 days of training ( Jose-Cunilleras et al, 2005 ). More recently, in a study with Alaskan sled dogs, an increase in GLUT4 protein expression was observed in the m. biceps femoris after 7 months of athletic conditioning ( Barrett and Scott Davis, 2023 ). Of interest is the fact that studies that report an increase in GLUT 4 expression in response to training, all start off with horses/dogs that were not involved in any type of daily exercise (for example horses in these studies were either box rested or paddock rested) prior to start of the study and encompass rather short periods of training, ranging from 3 days to 6 weeks ( McCutcheon et al, 2002 ; Lacombe et al, 2003 ; Jose-Cunilleras et al, 2005 ; Stewart-Hunt et al, 2006 ).…”

“…Muscle biopsies of the m. vastus lateralis were taken pre-and post-training at rest moments to determine total GLUT12 protein expression, which increased 104% in response to cycle training ( Stuart et al, 2010 ). Furthermore, in skeletal muscles of twelve Alaskan sled dogs, total GLUT12 protein expression was increased after 7 months of progressive endurance conditioning, while no significant change was measued in total GLUT8 protein expression ( Barrett and Scott Davis, 2023 ). In horses, only one study is available that determined total GLUT8 protein expression in skeletal muscles in response to AMPK activation.…”