Intact regulation of the AMPK signaling network in response to exercise and insulin in skeletal muscle of male patients with type 2 diabetes: Illumination of AMPK activation in recovery from exercise
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Intact regulation of the AMPK signaling network in response to exercise and insulin in skeletal muscle of male patients with type 2 diabetes : Illumination of AMPK activation in recovery from exercise. / Kjøbsted, Rasmus; Pedersen, Andreas J T; Hingst, Janne R; Sabaratnam, Rugivan; Birk, Jesper Bratz; Kristensen, Jonas Møller; Højlund, Kurt; Wojtaszewski, Jørgen.
In: Diabetes, Vol. 65, No. 5, 2016, p. 1219-1230.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Intact regulation of the AMPK signaling network in response to exercise and insulin in skeletal muscle of male patients with type 2 diabetes
T2 - Illumination of AMPK activation in recovery from exercise
AU - Kjøbsted, Rasmus
AU - Pedersen, Andreas J T
AU - Hingst, Janne R
AU - Sabaratnam, Rugivan
AU - Birk, Jesper Bratz
AU - Kristensen, Jonas Møller
AU - Højlund, Kurt
AU - Wojtaszewski, Jørgen
N1 - CURIS 2016 NEXS 110
PY - 2016
Y1 - 2016
N2 - Current evidence on exercise-mediated AMPK regulation in skeletal muscle of type 2 diabetic (T2D) patients is inconclusive. This may relate to inadequate segregation of trimer complexes in the investigation of AMPK activity. We examined the regulation of AMPK and downstream targets ACCβ, TBC1D1 and TBC1D4 in muscle biopsies obtained from thirteen overweight/obese T2D and fourteen weight-matched control male subjects before, immediately after and 3 h after exercise. Exercise increased AMPK α2β2γ3 activity and phosphorylation of ACCβ Ser(221), TBC1D1 Ser(237)/Thr(596) and TBC1D4 Ser(704). Conversely, exercise decreased AMPK α1β2γ1 activity and TBC1D4 Ser(318)/Thr(642) phosphorylation. Interestingly, compared to pre-exercise, 3 h into exercise recovery AMPK α2β2γ1 and α1β2γ1 activity were increased concomitant with increased TBC1D4 Ser(318)/Ser(341)/Ser(704) phosphorylation. No differences in these responses were observed between T2D and control subjects. Subjects were also studied by euglycemic-hyperinsulinemic clamps performed at rest and 3 h after exercise. We found no evidence for insulin to regulate AMPK activity. Thus, in muscle of T2D patients AMPK signaling is not compromised during exercise and insulin stimulation. Our results reveal a hitherto unrecognized activation of specific AMPK complexes in exercise recovery. We hypothesize that the differential regulation of AMPK complexes plays an important role for muscle metabolism and adaptations to exercise.
AB - Current evidence on exercise-mediated AMPK regulation in skeletal muscle of type 2 diabetic (T2D) patients is inconclusive. This may relate to inadequate segregation of trimer complexes in the investigation of AMPK activity. We examined the regulation of AMPK and downstream targets ACCβ, TBC1D1 and TBC1D4 in muscle biopsies obtained from thirteen overweight/obese T2D and fourteen weight-matched control male subjects before, immediately after and 3 h after exercise. Exercise increased AMPK α2β2γ3 activity and phosphorylation of ACCβ Ser(221), TBC1D1 Ser(237)/Thr(596) and TBC1D4 Ser(704). Conversely, exercise decreased AMPK α1β2γ1 activity and TBC1D4 Ser(318)/Thr(642) phosphorylation. Interestingly, compared to pre-exercise, 3 h into exercise recovery AMPK α2β2γ1 and α1β2γ1 activity were increased concomitant with increased TBC1D4 Ser(318)/Ser(341)/Ser(704) phosphorylation. No differences in these responses were observed between T2D and control subjects. Subjects were also studied by euglycemic-hyperinsulinemic clamps performed at rest and 3 h after exercise. We found no evidence for insulin to regulate AMPK activity. Thus, in muscle of T2D patients AMPK signaling is not compromised during exercise and insulin stimulation. Our results reveal a hitherto unrecognized activation of specific AMPK complexes in exercise recovery. We hypothesize that the differential regulation of AMPK complexes plays an important role for muscle metabolism and adaptations to exercise.
U2 - 10.2337/db15-1034
DO - 10.2337/db15-1034
M3 - Journal article
C2 - 26822091
VL - 65
SP - 1219
EP - 1230
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 5
ER -
ID: 154803848