Substrate Metabolism, Growth Hormone Signaling, and Insulin Sensitivity During Fasting
- Registration Number
- NCT02500095
- Lead Sponsor
- University of Aarhus
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 10
- healthy men
- written consent
- body mass index (BMI) 25-40
- age 20-60 years
- any kind of disease
- regular medication
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Fasting and saline Fasting 72 hours of fasting and concomitant saline Fasting and saline Saline 72 hours of fasting and concomitant saline Fasting and GHR blockade Fasting 72 hours of fasting and concomitant Growth hormone receptor (GHR) blockade with Pegvisomant (Somavert) for inhibition of the fasting-induced GH secretion Fasting and GHR blockade Pegvisomant 72 hours of fasting and concomitant Growth hormone receptor (GHR) blockade with Pegvisomant (Somavert) for inhibition of the fasting-induced GH secretion
- Primary Outcome Measures
Name Time Method 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. 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
- Secondary Outcome Measures
Name Time Method 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) Change in glucose metabolism assessed by tracer kinetics on every study day and by indirect calorimetry.
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) Method: Metabolomics
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) Change in protein metabolism assessed by tracer kinetics on every study day and by indirect calorimetry.
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) Change in fat metabolism assessed by tracer kinetics on every study day and by indirect calorimetry.
Trial Locations
- Locations (1)
Aarhus University Hospital
🇩🇰Aarhus, Denmark