Regulation of muscle glucose transport and GLUT-4 by nerve-derived factors and activity-related processes

Abstract

Glucose transport and GLUT-4 were examined in muscles in which activity and nerve-derived factors were eliminated (denervation) and in muscles in which only muscle activity was eliminated but in which nerve-derived factors were maintained [tetrodotoxin (TTX) treatment]. After 3 days of denervation, insulin-stimulated 3-O-methylglucose transport was markedly lowered in perfused rat hindlimb muscles (soleus, plantaris, and red and white gastrocnemius; < or = 35%). GLUT-4 was also decreased by 11-65% in denervated muscles. Blocking muscle activity with TTX superfusion of the sciatic nerve for 3 days reduced the insulin-stimulated glucose transport to the same extent as in the denervated muscles (P > 0.05). However, in soleus, plantaris, and red gastrocnemius muscles, GLUT-4 expression was reduced much less by TTX treatment than by denervation (P < 0.05). GLUT-4 mRNA abundance was decreased in denervated muscles but not in TTX-treated muscles. These results suggest that muscle activity largely regulates the insulin-signaling mechanisms of glucose transport and that nerve-derived trophic factors affect pretranslational events to regulate GLUT-4 expression.

Chronic Leptin Administration Decreases Fatty Acid Uptake and Fatty Acid Transporters in Rat Skeletal Muscle

“…Similarly, in CD36 null mice, a greater reduction in fatty acid uptake occurred in oxidative muscles than in glycolytic muscles (45). When we examined the effects of reduced muscle activity (denervation) on the changes in glucose transport and transporters (46,47) and lactate transport (48) and monocarboxylate transporters (49), the greatest effects were also observed in the more oxidative types of muscles. Thus, it appears that oxidative types of skeletal muscle are more susceptible to alterations in their substrate transport capacities and transporter expression than glycolytic muscles.…”

Isoform-specific regulation of the lactate transporters MCT1 and MCT4 by contractile activity

“…A number of studies in recent years have shown that increased muscle contractile activity induced by chronic muscle stimulation regulates the expression of the glucose transporter GLUT-4 (17,20,23,48) and the fatty acid transporter fatty acid translocase (3). All of these transporters, as well as MCT1, are highly correlated with the oxidative capacity of different muscles (20,30,31,34,35). This facilitates a greater rate of uptake of glucose, fatty acid, and lactate by oxidative muscles (20,30,31,34,35), where these substrates can be readily oxidized in these muscles (3,7,37).…”

“…All of these transporters, as well as MCT1, are highly correlated with the oxidative capacity of different muscles (20,30,31,34,35). This facilitates a greater rate of uptake of glucose, fatty acid, and lactate by oxidative muscles (20,30,31,34,35), where these substrates can be readily oxidized in these muscles (3,7,37). To facilitate the oxidative disposal of lactate, MCT1 proteins are perhaps concentrated at the surface of the muscle clustered near mitochondria.…”

Persistence of myosin heavy chain-based fiber types in innervated but silenced rat fast muscle

“…Many muscle adaptations to denervation are reminiscent of developmental processes. 6,16,19,31 Several studies have reported a larger effect of denervation on muscle properties than TTX treatment, 33,34 suggesting that activity-independent processes, e.g., axonal transport, play a role in the regulation of muscle properties. Recently, however, Buffeli et al 4 have shown that if a high enough level of TTX is used, the effects of 4-5 weeks of TTX administration or denervation on the muscle weight, contractile properties, and fiber type composition of the soleus or extensor digitorum longus (EDL) are similar.…”