Contraction-Mediated Glucose Transport in Skeletal Muscle Is Regulated by a Framework of AMPK, TBC1D1/4, and Rac1.
| Autor: | de Wendt, Christian, Espelage, Lena, Eickelschulte, Samaneh, Springer, Christian, Toska, Laura, Scheel, Anna, Bedou, Awovi Didi, Benninghoff, Tim, Cames, Sandra, Stermann, Torben, Chadt, Alexandra, Al-Hasani, Hadi |
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| Předmět: |
SKELETAL muscle
GLUCOSE LABORATORY mice AEROBIC capacity SOLEUS muscle GLUCOSE metabolism PROTEIN metabolism PROTEINS RESEARCH MUSCLE contraction BIOLOGICAL transport AMP-activated protein kinases ANIMAL experimentation NEUROPEPTIDES RESEARCH methodology PHYSICAL fitness EVALUATION research CELLULAR signal transduction COMPARATIVE studies MICE |
| Zdroj: | Diabetes; Dec2021, Vol. 70 Issue 12, p2796-2809, 14p |
| Abstrakt: | The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4, both substrates for AMPK, play important roles in exercise metabolism and contraction-dependent translocation of GLUT4 in skeletal muscle. However, the specific contribution of each RabGAP in contraction signaling is mostly unknown. In this study, we investigated the cooperative AMPK-RabGAP signaling axis in the metabolic response to exercise/contraction using a novel mouse model deficient in active skeletal muscle AMPK combined with knockout of either Tbc1d1, Tbc1d4, or both RabGAPs. AMPK deficiency in muscle reduced treadmill exercise performance. Additional deletion of Tbc1d1 but not Tbc1d4 resulted in a further decrease in exercise capacity. In oxidative soleus muscle, AMPK deficiency reduced contraction-mediated glucose uptake, and deletion of each or both RabGAPs had no further effect. In contrast, in glycolytic extensor digitorum longus muscle, AMPK deficiency reduced contraction-stimulated glucose uptake, and deletion of Tbc1d1, but not Tbc1d4, led to a further decrease. Importantly, skeletal muscle deficient in AMPK and both RabGAPs still exhibited residual contraction-mediated glucose uptake, which was completely abolished by inhibition of the GTPase Rac1. Our results demonstrate a novel mechanistic link between glucose transport and the GTPase signaling framework in skeletal muscle in response to contraction. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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