TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction
| Autor: | Rasmus Kjøbsted, Jonas M. Kristensen, Nicolas O. Eskesen, Kohei Kido, Klara Fjorder, Ditte F. Damgaard, Jeppe K. Larsen, Nicoline R. Andersen, Jesper B. Birk, Anders Gudiksen, Jonas T. Treebak, Peter Schjerling, Henriette Pilegaard, Jørgen F. P. Wojtaszewski |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Kjøbsted, R, Kristensen, J M, Eskesen, N O, Kido, K, Fjorder, K, Damgaard, D F, Larsen, J K, Andersen, N R, Birk, J B, Gudiksen, A, Treebak, J T, Schjerling, P, Pilegaard, H & Wojtaszewski, J 2023, ' TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction ', Diabetes, vol. 72, no. 7, pp. 857-871 . https://doi.org/10.2337/db22-0666 |
| Popis: | The ability of insulin to stimulate glucose uptake in skeletal muscle is important for whole-body glycemic control. Insulin-stimulated skeletal muscle glucose uptake is improved in the period after a single bout of exercise and accumulating evidence suggests that phosphorylation of TBC1D4 by the protein kinase AMPK is the primary mechanism responsible for this phenomenon. To investigate this, we generated a TBC1D4 knock-in mouse model with a serine-to-alanine point mutation at residue 711 that is phosphorylated in response to both insulin and AMPK activation. Female TBC1D4-S711A mice exhibited normal growth and eating behavior as well as intact wholebody glycemic control on chow and high-fat diets. Moreover, muscle contraction increased glucose uptake, glycogen utilization and AMPK activity similarly in wild-type and TBC1D4-S711A mice. In contrast, improvements in whole-body and muscle insulin sensitivity after exercise and contractions were only evident in wild-type mice and occurred concomitantly with enhanced phosphorylation of TBC1D4-S711. These results provide genetic evidence to support that TBC1D4-S711 serves as a major point of convergence for AMPK- and insulin-induced signaling that mediates the insulin-sensitizing effect of exercise and contractions on skeletal muscle glucose uptake. |
| Databáze: | OpenAIRE |
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