Effect of Exercise Intensity on Skeletal Muscle AMPK Signaling in Humans

Abstract

The effect of exercise intensity on skeletal muscle AMP-activated protein kinase (AMPK) signaling and substrate metabolism was examined in eight men cycling for 20 min at each of three sequential intensities: low (40 ؎ 2% VO 2 peak), medium (59 ؎ 1% VO 2 peak), and high (79 ؎ 1% VO 2 peak). Muscle free AMP/ATP ratio only increased at the two higher exercise intensities (P < 0.05). AMPK ␣1 (1.5-fold) and AMPK ␣2 (5-fold) activities increased from low to medium intensity, with AMPK ␣2 activity increasing further from medium to high intensity. The upstream AMPK kinase activity was substantial at rest and only increased 50% with exercise, indicating that, initially, signaling through AMPK did not require AMPK kinase posttranslational modification. Acetyl-CoA carboxylase (ACC)-␤ phosphorylation was sensitive to exercise, increasing threefold from rest to low intensity, whereas neuronal NO synthase (nNOS) phosphorylation was only observed at the higher exercise intensities. Glucose disappearance (tracer) did not increase from rest to low intensity, but increased sequentially from low to medium to high intensity. Calculated fat oxidation increased from rest to low intensity in parallel with ACC␤ phosphorylation, then declined during high intensity. These results indicate that ACC␤ phosphorylation is especially sensitive to exercise and tightly coupled to AMPK signaling and that AMPK activation does not depend on AMPK kinase activation during exercise.

High-fat diet overrules the effects of training on fiber-specific intramyocellular lipid utilization during exercise

“…3) and as such, may be regarded as a confirmation of the AMPK findings. The lower ACC␤ phosphorylation immediately after exercise post-training likely results from a decreased relative exercise intensity rather than being an indication of fat oxidation during exercise (10), also supported by our previous data (16a, 62). Surprisingly, we found PDK4 mRNA content pre-and postexercise to be decreased in F but not in CHO or in CON (see Fig.…”

Effect of exercise intensity and AICAR on isoform-specific expressions of murine skeletal muscle PGC-1α mRNA: a role of β2-adrenergic receptor activation

“…AMPK phosphorylates PGC-1␣ protein directly and activates the promoter activity of PGC-1␣ (17). Because activation of AMPK was observed after exercise in skeletal muscle (5,42), AMPK might be involved in increased expression of PGC-1␣ mRNAs after exercise. Gastrocnemius was obtained just after treadmill running at 10, 20, or 30 m/min for 30 min, and AMPK activity was measured.…”

“…These data indicate that ␤ 2 -AR activation is a major mechanism in the increase in PGC-1␣ expression in skeletal muscles and that the increase in PGC-1␣ mRNAs is isoform specific. However, it is not known which isoform of PGC-1␣ was increased in response to the high-intensity exercise, by which ␣2-AMPK was markedly activated (5,42). Therefore, in the present study, we examined the effects of exercise intensity on increases and contributions of AMPK to isoform-specific increase of PGC-1␣ mRNA.…”

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

“…It has been postulated that NO and AMPK are part of the same signalling pathway. During exercise, AMPK phosphorylates nNOSμ in human skeletal muscle [46][47][48], while in rat skeletal muscle glucose uptake stimulated by the AMP analogue, 5-aminoimidazole-4-carboxamide ribonucleoside, which activates AMPK, can be blocked by an NOS inhibitor [49]. Further studies are required to clarify the relationship between NO and AMPK with regard to glucose uptake.…”