TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction. / Kjøbsted, Rasmus; Kristensen, Jonas Møller; Eskesen, Nicolas Oldenburg; Kido, Kohei; Fjorder, Klara; Damgaard, Ditte F; Larsen, Jeppe Kjærgaard; Andersen, Nicoline Resen; Birk, Jesper Bratz; Gudiksen, Anders; Treebak, Jonas Thue; Schjerling, Peter; Pilegaard, Henriette; Wojtaszewski, Jørgen.

I: Diabetes, Bind 72, Nr. 7, 2023, s. 857-871.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Kjøbsted, R, Kristensen, JM, Eskesen, NO, Kido, K, Fjorder, K, Damgaard, DF, Larsen, JK, Andersen, NR, Birk, JB, Gudiksen, A, Treebak, JT, Schjerling, P, Pilegaard, H & Wojtaszewski, J 2023, 'TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction', Diabetes, bind 72, nr. 7, s. 857-871. https://doi.org/10.2337/db22-0666

APA

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, 72(7), 857-871. https://doi.org/10.2337/db22-0666

Vancouver

Kjøbsted R, Kristensen JM, Eskesen NO, Kido K, Fjorder K, Damgaard DF o.a. TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction. Diabetes. 2023;72(7):857-871. https://doi.org/10.2337/db22-0666

Author

Kjøbsted, Rasmus ; Kristensen, Jonas Møller ; Eskesen, Nicolas Oldenburg ; Kido, Kohei ; Fjorder, Klara ; Damgaard, Ditte F ; Larsen, Jeppe Kjærgaard ; Andersen, Nicoline Resen ; Birk, Jesper Bratz ; Gudiksen, Anders ; Treebak, Jonas Thue ; Schjerling, Peter ; Pilegaard, Henriette ; Wojtaszewski, Jørgen. / TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction. I: Diabetes. 2023 ; Bind 72, Nr. 7. s. 857-871.

Bibtex

@article{0b96b3181bed4effb82230f5fe36fc88,

title = "TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction",

abstract = "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.",

keywords = "Faculty of Science, AS160, AMPK, Exercise, Glucose uptake, Insulin sensitivity",

author = "Rasmus Kj{\o}bsted and Kristensen, {Jonas M{\o}ller} and Eskesen, {Nicolas Oldenburg} and Kohei Kido and Klara Fjorder and Damgaard, {Ditte F} and Larsen, {Jeppe Kj{\ae}rgaard} and Andersen, {Nicoline Resen} and Birk, {Jesper Bratz} and Anders Gudiksen and Treebak, {Jonas Thue} and Peter Schjerling and Henriette Pilegaard and J{\o}rgen Wojtaszewski",

note = "{\textcopyright} 2023 by the American Diabetes Association.",

year = "2023",

doi = "10.2337/db22-0666",

language = "English",

volume = "72",

pages = "857--871",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "7",

}

RIS

TY - JOUR

T1 - TBC1D4-S711 controls skeletal muscle insulin sensitization after exercise and contraction

AU - Kjøbsted, Rasmus

AU - Kristensen, Jonas Møller

AU - Eskesen, Nicolas Oldenburg

AU - Kido, Kohei

AU - Fjorder, Klara

AU - Damgaard, Ditte F

AU - Larsen, Jeppe Kjærgaard

AU - Andersen, Nicoline Resen

AU - Birk, Jesper Bratz

AU - Gudiksen, Anders

AU - Treebak, Jonas Thue

AU - Schjerling, Peter

AU - Pilegaard, Henriette

AU - Wojtaszewski, Jørgen

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Faculty of Science

KW - AS160

KW - AMPK

KW - Exercise

KW - Glucose uptake

KW - Insulin sensitivity

U2 - 10.2337/db22-0666

DO - 10.2337/db22-0666

M3 - Journal article

C2 - 37074686

VL - 72

SP - 857

EP - 871

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 7

ER -

ID: 344644780

Biomedicinsk Institut