A Single Dose of Prednisolone as a Modulator of Undercarboxylated Osteocalcin and Insulin Sensitivity Post-Exercise in Healthy Young Men: A Study Protocol.

Andrew Garnham,Nigel K Stepto,George Jerums,Itamar Levinger,Lewan Parker,Ego Seeman,David L Hare,Glenn K Mcconell,Peter R Ebeling,Mitchell Anderson,Tara C Brennan-Speranza

doi:10.2196/resprot.5119

Abstract

BackgroundUndercarboxylated osteocalcin (ucOC) increases insulin sensitivity in mice. In humans, data are supportive, but the studies are mostly cross-sectional. Exercise increases whole-body insulin sensitivity, in part via ucOC, while acute glucocorticoid treatment suppresses ucOC in humans and mice.ObjectivesA single dose of prednisolone reduces the rise in ucOC produced by exercise, which partly accounts for the failed increase in insulin sensitivity following exercise.MethodsHealthy young men (n=12) aged 18 to 40 years will be recruited. Initial assessments will include analysis of fasting blood, body composition, aerobic power (VO2peak), and peak heart rate. Participants will then be randomly allocated, double-blind, to a single dose of 20 mg of prednisolone or placebo. The two experimental trials will involve 30 minutes of interval exercise (90%-95% peak heart rate), followed by 3 hours of recovery and 2 hours of euglycaemic- hyperinsulinaemic clamp (insulin clamp). Seven muscle biopsies and blood samples will be obtained at rest, following exercise and post-insulin clamps.ResultsThe study is funded by the National Heart Foundation of Australia and Victoria University. Enrollment has already commenced and data collection will be completed in 2016.ConclusionIf the hypothesis is confirmed, the study will provide novel insights into the potential role of ucOC in insulin sensitivity in human subjects and will elucidate pathways involved in exercise-induced insulin sensitivity.

Highlights

Insulin resistance is characterized by impaired insulin action in target tissues
The sample size is based on our previous work where exercise significantly increased Undercarboxylated osteocalcin (ucOC) by approximately 6.5% and insulin sensitivity by approximately 35% during a euglycaemic-hyperinsulinaemic clamp (n=11) [7,12]
If this study shows that suppression of ucOC with a single dose of prednisolone leads to suppression of insulin sensitivity post exercise, this suggests that ucOC is likely to participate in the modulation of insulin sensitivity in humans

Summary

Introduction

Insulin resistance is characterized by impaired insulin action in target tissues. Skeletal muscle is a major site of glucose uptake and disposal in response to insulin and skeletal muscle can become insulin resistant in obese individuals and those with type 2 diabetes mellitus (T2DM). The skeleton is partly involved in determining insulin secretion, insulin sensitivity, and glucose tolerance via the undercarboxylated form of osteocalcin (ucOC) [1,2]. UcOC- deficient mice have insulin resistance and in obese mice recombinant ucOC treatment reduces glucose levels and increases insulin secretion and sensitivity [2,3]. A lower serum ucOC is associated with a higher fasting glucose and fat mass, and lower insulin sensitivity [7,8]. This suggests ucOC participates in glucose homeostasis in humans; prospective interventional studies are required [9]. Exercise increases whole-body insulin sensitivity, in part via ucOC, while acute glucocorticoid treatment suppresses ucOC in humans and mice. Conclusion: If the hypothesis is confirmed, the study will provide novel insights into the potential role of ucOC in insulin sensitivity in human subjects and will elucidate pathways involved in exercise-induced insulin sensitivity

Objectives

Methods

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Conclusion