Substrate Metabolism, Growth Hormone Signaling, and Insulin Sensitivity During Fasting in Overweight and Obese Human Subjects and the Impact of Growth Hormone Receptor Blockade
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins and CHANGE in messenger ribonucleic acid (mRNA) expression of target genes in muscle- and fat-tissue.
研究概览
简要总结
Background: Calorie restriction increases longevity in many species and attenuate the development of chronic disorders including type 2 diabetes, cardiovascular diseases and cancer. In mice reduced activity of insulin-like growth factor I (IGF-I) and/or insulin is associated with extended longevity. Growth hormone (GH) is the main regulator of IGF-I production, but the molecular mechanism whereby GH switches from IGF-I stimulation (protein anabolism) to fatty acid oxidation (fatty acid catabolism) as well as induction of insulin resistance during fasting remains enigmatic.
Hypotheses: The changes of the global set of metabolites, induction of insulin resistance, and the shift in metabolism from protein anabolism to lipolysis together with the potentially favorable effect of calorie restriction during fasting depend on preserved fasting-induced GH secretion.
Aim: The investigators wish to provide knowledge on changes in metabolites and shift in signaling pathways that take place at the transition to the fasting state among healthy overweight and obese subjects. Furthermore the investigators wish to determine the effect of GH on the adaption of the metabolism to a fasting state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •healthy men
- •written consent
- •body mass index (BMI) 25-40
- •age 20-60 years
排除标准
- •any kind of disease
- •regular medication
研究组 & 干预措施
Fasting and saline
72 hours of fasting and concomitant saline
干预措施: Fasting (Other)
Fasting and saline
72 hours of fasting and concomitant saline
干预措施: Saline (Drug)
Fasting and GHR blockade
72 hours of fasting and concomitant Growth hormone receptor (GHR) blockade with Pegvisomant (Somavert) for inhibition of the fasting-induced GH secretion
干预措施: Fasting (Other)
Fasting and GHR blockade
72 hours of fasting and concomitant Growth hormone receptor (GHR) blockade with Pegvisomant (Somavert) for inhibition of the fasting-induced GH secretion
干预措施: Pegvisomant (Drug)
结局指标
主要结局
Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins and CHANGE in messenger ribonucleic acid (mRNA) expression of target genes in muscle- and fat-tissue.
时间窗: Muscle and fat biopsies obtained at t1= 9.00 am (60 min) and t2=12.30 am (270 min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days)
Change in phosphorylation of target proteins and mRNA expression of target genes
次要结局
- Glucose metabolism(Change in glucose metabolism using glucose tracer from t=0 min - 360 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days))
- Magnetic resonance (MR) spectroscopy(During fasting: t= 12 hours and t= 48 hours of fasting)
- Change in concentrations of metabolites in the insulin and growth hormone signaling pathways using metabolomics(Muscle-tissue obtained at t1= 9.00 am (60 min) and t2=12.30 am (270min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days))
- Protein metabolism(Change in protein metabolism using urea tracer from t=0 min - 240 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days))
- Fat metabolism(Change in fat metabolism using palmitic acid tracer from t1=180 min - 240 min and t2=300 min - 360 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days))