Lipolytic Effects of GH in Hypopituitary Patients in Vivo: Molecular Mechanisms and Temporal Patterns.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Lipolytic activity measured as area under the curve (AUC) for FFA (free fatty acid) before and during clamp-conditions.
研究概览
简要总结
Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric restriction GH predominantly promotes fat metabolism.
GH counteracts the effect of insulin in many tissues, of which insulin-stimulated glucose uptake in skeletal muscle has been most extensively studied. Substrate competition between elevated free fatty acids and glucose is suggested as a mechanism, and this hypothesis can be tested mechanistically by means of acipimox, which is a nicotinic acid that suppresses the fat metabolizing effects of GH.
The hypothesis is, that the suppressive effect of GH on insulin-stimulated glucose uptake in skeletal muscle is obviated by acipimox-induced inhibition of fat metabolism.
In order to investigate this, eight adult hypopituitary patients with documented GH-deficiency will be studied in the presence and absence of GH and acipimox, respectively, and biopsies from skeletal muscle and subcutaneous adipose tissue will be analyzed.
Knowledge of the effects of growth hormone and fat metabolism can in shot-sight as well as in long-sight have great importance for the understanding of growth disorders from overweight and type 2 diabetes to malnutrition and eating disorders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •hypopituitary patients with documented GH-deficiency
排除标准
- •other significant disease
研究组 & 干预措施
Acipimox/GH substitution
Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Continue GH substitution as usually.
干预措施: Acipimox (Drug)
Acipimox/GH substitution
Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Continue GH substitution as usually.
干预措施: GH substitution (Drug)
Acipimox/GH pause
Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Pause GH substitution to days prior to the study day.
干预措施: Acipimox (Drug)
Acipimox/GH pause
Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Pause GH substitution to days prior to the study day.
干预措施: GH pause (Other)
Placebo/GH substitution
Drug: Placebo tablets Continue GH substitution as usually.
干预措施: Placebo (Drug)
Placebo/GH substitution
Drug: Placebo tablets Continue GH substitution as usually.
干预措施: GH substitution (Drug)
Placebo/GH pause
Drug: Placebo tablets Pause GH substitution to days prior to the study day.
干预措施: Placebo (Drug)
Placebo/GH pause
Drug: Placebo tablets Pause GH substitution to days prior to the study day.
干预措施: GH pause (Other)
结局指标
主要结局
Lipolytic activity measured as area under the curve (AUC) for FFA (free fatty acid) before and during clamp-conditions.
时间窗: 1 year
次要结局
- GH signaling proteins and gene targets in adipose and skeletal muscle tissues measured by western blotting and qPCR(1,5 years)
- Insulin sensitivity as measured by M value and GIR (glucose infusion rate)(6 months)
- Substrate metabolism as measured by indirect calorimetry, tritiated glucose and circulating hormones and metabolites(1 year)
- PDH (pyruvate dehydrogenase) activity in skeletal muscle measured by an PDH activity assay(1 year)