Exercise improves phosphatidylinositol-3,4,5-trisphosphate responsiveness of atypical protein kinase C and interacts with insulin signalling to peptide elongation in human skeletal muscle.
We investigated if acute endurance-type exercise interacts with insulin-stimulated activation of atypical protein kinase C (aPKC) and insulin signalling to peptide chain elongation in human skeletal muscle. Four hours after acute one-legged exercise, insulin-induced glucose uptake was approximately 80% higher (N = 12, P < 0.05) in previously exercised muscle, measured during a euglycaemic-hyperinsulinaemic clamp (100 microU ml(-1)). Insulin increased (P < 0.05) both insulin receptor substrate (IRS)-1 and IRS-2 associated phosphatidylinositol (PI)-3 kinase activity and led to increased (P < 0.001) phosphorylation of Akt on Ser(473) and Thr(308) in skeletal muscle. Interestingly, in response to prior exercise IRS-2-associated PI-3 kinase activity was higher (P < 0.05) both at basal and during insulin stimulation. This coincided with correspondingly altered phosphorylation of the extracellular-regulated protein kinase 1/2 (ERK 1/2), p70S6 kinase (P70S6K), eukaryotic elongation factor 2 (eEF2) kinase and eEF2. aPKC was similarly activated by insulin in rested and exercised muscle, without detectable changes in aPKC Thr(410) phosphorylation. However, when adding phosphatidylinositol-3,4,5-triphosphate (PIP3), the signalling product of PI-3 kinase, to basal muscle homogenates, aPKC was more potently activated (P = 0.01) in previously exercised muscle. Collectively, this study shows that endurance-type exercise interacts with insulin signalling to peptide chain elongation. Although protein turnover was not evaluated, this suggests that capacity for protein synthesis after acute endurance-type exercise may be improved. Furthermore, endurance exercise increased the responsiveness of aPKC to PIP3 providing a possible link to improved insulin-stimulated glucose uptake after exercise.
Frøsig
Christian
C
Copenhagen Muscle Research Centre, Section of Human Physiology, Department of Exercise and Sport Sciences, University of Copenhagen, 13, Universitetsparken, DK-2100, Copenhagen, Denmark.
Sajan
Mini P
MP
Maarbjerg
Stine J
SJ
Brandt
Nina
N
Roepstorff
Carsten
C
Wojtaszewski
Jørgen F P
JF
Kiens
Bente
B
Farese
Robert V
RV
Richter
Erik A
EA
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D007773:Lactates / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D010441:Peptide Chain Elongation, Translational; D018129:Phosphatidylinositol Phosphates / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
D001786:Blood Glucose; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007773:Lactates; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D011493:Protein Kinase C