TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Indsendt manuskript, 26,2 MB, PDF-dokument
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.
|Status||Udgivet - 2023|
CURIS 2023 NEXS 147
© 2023 by the American Diabetes Association.
- Det Natur- og Biovidenskabelige Fakultet
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk