Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Glucocorticoid induced suppression of osteocalcin is associated with attenuated post-exercise insulin sensitivity and impaired skeletal muscle mTOR and insulin signaling in humans. (#61)

Lewan Parker 1 , Andrew Garnham 2 , Glenn McConell 1 , Nigel Stepto 1 , David Hare 3 , Elizabeth Byrnes 4 , Peter Ebeling 5 , Ego Seeman 6 , Tara Brennan-Speranza 7 , Itamar Levinger 1
  1. Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, VIC, Australia
  2. School of Exercise & Nutrition Sciences, Deakin University, Melbourne, VIC, Australia
  3. University of Melbourne and the Department of Cardiology, Austin Health, Melbourne, VIC, Australia
  4. PathWest QEII Medical Centre, Perth, WA, Australia
  5. Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia
  6. Department of Endocrinology, University of Melbourne and Austin Health, Melbourne, VIC, Australia
  7. Department of Physiology, University of Sydney, Sydney, NSW, Australia

Purpose. Glucocorticoid (GC) treatment impairs osteoblast function, undercarboxylated osteocalcin (ucOC), and insulin sensitivity. However, the effects of acute GC ingestion on post-exercise insulin sensitivity in humans are unclear. We investigated whether the suppression of ucOC, by a single dose of GC (prednisolone), would be associated with impaired post-exercise insulin sensitivity and skeletal muscle mTOR/insulin protein signalling. Methods. Nine healthy males (Age: 28 ± 2 years; BMI: 24 ± 1; Mean ± SEM) were randomly allocated in a double-blinded cross-over design to ingest a single dose of prednisolone (20 mg) and placebo, ~7 days between trials. Twelve hours after capsule ingestion, after an overnight fast, participants performed a session of high-intensity interval exercise (4 x 4-minute cycling intervals at 90-95% HRpeak, 2-minute active recovery periods). The homeostatic model assessment (HOMA2-IR) was used to assess resting insulin resistance and the euglycaemic-hyperinsulinaemic clamp (EHC) was used to assess insulin sensitivity 5 hours after exercise. Serum ucOC, and skeletal muscle AS160Thr642, AktSer473 and mTORSer2481 protein phosphorylation, were measured at baseline and post-EHC. Results. Compared to placebo, prednisolone treatment suppressed ucOC at baseline (-24±2%, p<0.001) and post-EHC (-18±2%), which coincided with increased HOMA2-IR (107±27%, p<0.001) and decreased post-exercise insulin sensitivity (-34±5%, p<0.001). Higher serum ucOC was associated with lower HOMA2-IR (r=-0.54, p<0.05) and greater post-exercise insulin sensitivity (r=0.72, p<0.01). Prednisolone significantly impaired (p<0.05) the post-exercise insulin stimulated increase in skeletal muscle AS160Thr642 (~-50%), AktSer473 (~-61%) and mTORSer2481 (~-59%) phosphorylation, which significantly correlated (p<0.01) with lower serum ucOC (r=0.64, r=0.71 and r=0.61, respectively) and post-exercise insulin sensitivity (r=0.56, r=0.75, r=0.54, respectively). Conclusions. The negative effect of prednisolone on insulin sensitivity at rest and following exercise are related, at least in part, to the suppression of ucOC and mTOR/insulin signalling. Targeting ucOC mediated signalling pathways in humans may prove to be an effective intervention for improving glycaemic control in insulin resistant populations.