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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.

Authors :
Kjøbsted, Rasmus
Pedersen, Andreas J.T.
Hingst, Janne R.
Sabaratnam, Rugivan
Birk, Jesper B.
Kristensen, Jonas M.
Højlund, Kurt
Wojtaszewski, Jørgen F.P.
Source :
Diabetes; May2016, Vol. 65 Issue 5, p1219-1230, 12p, 1 Diagram, 1 Chart, 5 Graphs
Publication Year :
2016

Abstract

Current evidence on exercise-mediated AMPK regulation in skeletal muscle of patients with type 2 diabetes (T2D) is inconclusive. This may relate to inadequate segregation of trimeric complexes in the investigation of AMPK activity. We examined the regulation of AMPK and downstream targets ACC-β, TBC1D1, and TBC1D4 in muscle biopsy specimens obtained from 13 overweight/obese patients with T2D and 14 weight-matched male control 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 with preexercise, 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 patients with 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, AMPK signaling is not compromised in muscle of patients with T2D 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00121797
Volume :
65
Issue :
5
Database :
Complementary Index
Journal :
Diabetes
Publication Type :
Academic Journal
Accession number :
114741057
Full Text :
https://doi.org/10.2337/db15-1034