Proceedings of The Physiological Society
King's College London (2009) Proc Physiol Soc 14, PC41
Myokine responses to an acute bout of resistance exercise in rat
D. L. Hamilton1, A. Philp1, G. Hardie1, K. Baar1, M. Towler1
1. Molecular Physiology, University of Dundee, Dundee, United Kingdom.
Skeletal muscle has recently been identified as an important endocrine organ, which independently produces a group of cytokines, now termed myokines. Recent work from our lab identified that an acute bout of unilateral resistance exercise can systemically modulate the responsiveness of skeletal muscle insulin signalling to an IP bolus of insulin (10mU/g BW). To investigate this further we exposed rats to a single bout of unilateral resistance exercise via sciatic nerve stimulation under inhaled anaesthetic (2.5% Isoflourane vaporised in 100% oxygen at 1.5L/min) followed by an insulin tolerance test under inhaled anaesthetic 48hrs later. The exercised animals had a trend to lower postprandial blood glucose compared to the sham operated controls (Sham = 7.55 ± 0.22 mmol/L, Ex = 7.15 ± 0.22 mmol/L) and there was a trend for blood glucose to be lower at all other time points. In the livers of exercised animals, S6K1 Thr389 phosphorylation was significantly elevated [Con = 0.18 ± 0.04, sham = 0.47 ±0.09, Ex = 1.01 ± 0.09 (n=4, Tukey’s HSD test)] there was also a trend for PKB Thr308 phosphorylation to be elevated in the Ex group above that of the Sham group. We profiled a range of myokines at the mRNA level using qPCR over a time course following a single bout of unilateral resistance exercise. IL18 was significantly elevated at 18 [200.47 ± 50.50% (t-test)] and 48hrs [121.95 ± 56.58% (t-test)] and the caspase responsible for cleaving pro-IL18, Caspase-1, was also significantly elevated at 48hrs [48.04 ± 14.12% (t-test)] following exercise. Treatment of C2C12 cells with IL18 for 24hrs significantly elevated insulin (100nM) stimulated PKB Thr308 [vehicle + con = 0.84 ± 0.09, vehicle + Ins = 3.97 ± 0.34, IL18 + con = 0.68 ± 0.32, IL18 + Ins = 5.18 ± 0.10 (n=3, Tukey’s HSD test)] phosphorylation and led to increased insulin stimulated glucose uptake [vehicle + Ins = 2.94 ± 0.17, IL18 + Ins = 3.61 ± 0.45 (n=4, Tukey’s HSD test). To conclude resistance exercise recruiting approximately 2% of the animal’s body mass leads to a systemic modulation in insulin stimulated signalling, which may be mediated by the myokine IL18.
Where applicable, experiments conform with Society ethical requirements