Serum is not necessary for prior pharmacological activation of AMPK to increase insulin sensitivity of mouse skeletal muscle

TY - JOUR

T1 - Serum is not necessary for prior pharmacological activation of AMPK to increase insulin sensitivity of mouse skeletal muscle

AU - Jørgensen, Nicolas Oldenburg

AU - Wojtaszewski, Jørgen

AU - Kjøbsted, Rasmus

N1 - CURIS 2018 NEXS 156

PY - 2018/4/15

Y1 - 2018/4/15

N2 - Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4) Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

AB - Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4) Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

KW - Faculty of Science

KW - Exercise

KW - Glucose uptake

KW - AMP-activated protein kinase

KW - TBC1D4

KW - AS160

U2 - 10.3390/ijms19041201

DO - 10.3390/ijms19041201

M3 - Journal article

C2 - 29662023

SN - 1661-6596

VL - 19

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

IS - 4

M1 - 1201

ER -