Levinger Itamar, Brennan-Speranza Tara C, Stepto Nigel K, Jerums George, Parker Lewan, McConell Glenn K, Anderson Mitchell, Garnham Andrew, Hare David L, Ebeling Peter R, Seeman Ego
Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.
JMIR Res Protoc. 2016 Jun 3;5(2):e78. doi: 10.2196/resprot.5119.
Undercarboxylated 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.
A single dose of prednisolone reduces the rise in ucOC produced by exercise, which partly accounts for the failed increase in insulin sensitivity following exercise.
Healthy 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.
The 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.
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.
羧化不足的骨钙素（ucOC）可提高小鼠的胰岛素敏感性。在人类中，有数据支持这一观点，但研究大多为横断面研究。运动可提高全身胰岛素敏感性，部分是通过ucOC实现的，而急性糖皮质激素治疗会抑制人类和小鼠体内的ucOC。
单剂量泼尼松龙可降低运动引起的ucOC升高，这部分解释了运动后胰岛素敏感性未能增加的原因。
将招募18至40岁的健康年轻男性（n = 12）。初始评估将包括空腹血液分析、身体成分、有氧能力（VO2峰值）和心率峰值。然后，参与者将被随机、双盲地分配到单剂量20 mg泼尼松龙或安慰剂组。两项实验性试验将包括30分钟的间歇运动（心率峰值的90%-95%），随后是3小时的恢复和2小时的正常血糖-高胰岛素钳夹（胰岛素钳夹）。在静息状态、运动后和胰岛素钳夹后将采集七次肌肉活检样本和血液样本。
该研究由澳大利亚国家心脏基金会和维多利亚大学资助。招募工作已经开始，数据收集将于2016年完成。
如果该假设得到证实，该研究将为ucOC在人类胰岛素敏感性中的潜在作用提供新的见解，并将阐明运动诱导胰岛素敏感性所涉及的途径。
