Substrate Metabolism, Growth Hormone Signaling (GH), and Insulin Sensitivity During GH and Ketone Bodies Infusion
Study Details
Study Description
Brief Summary
Background: Humans naturally produce ketone bodies under daily living conditions. The main ketone bodies are two functioning acids, beta-hydroxybutyric acid (3-OHB) and acetoacetate, and the pH-neutral, but odorous, acetone. In the fed state, level of 3-OHB is suppressed to an almost unmeasurable level while, in the fasted state, it rises to 0.1-0.5 millimoles (mM). Main regulation of ketone synthesis is the abundance of sugars and resulting adaptations in insulin secretion. Thus, ketone bodies are formed when sugar is not readily available and insulin is suppressed. This picture is, to a certain degree, seen in acute inflammatory states and, indeed, during starvation, where level of 3-OHB increases to 5-8 mM.
Hypothesis:
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Ketone bodies changes the insulin sensitivity and substrate metabolism in human subjects
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Ketone bodies changes the GH signaling in muscle and adipose tissue
Aim: The investigators wish to provide knowledge on changes in metabolites and shift in signaling pathways and insulin sensitivity during GH infusion and concomitant ketone bodies infusion among healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Control 12 hours of fasting |
|
| Experimental: GH infusion 12 hours of fasting |
Drug: Somatropin
Somatropin infusion (Genotropin®)
|
| Experimental: GH and ketone bodies infusion 12 hours of fasting |
Drug: Somatropin
Somatropin infusion (Genotropin®)
Other: Ketone bodies
ketone bodies infusion
|
Outcome Measures
Primary Outcome Measures
- Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins 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 using Western Blotting (WB)
Secondary Outcome Measures
- 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.
- Insulin and growth hormone signaling, expressed as 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 mRNA expression of target genes using Polymerase Chain Reaction (PCR).
- Investigation of the balance in the autonomic nervous system [Measurement of heart rate variability at t1=10.30 am(150 min) and 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.]
Heart rate variability (the study of beat-to-beat fluctuations in heart rate).
Eligibility Criteria
Criteria
Inclusion Criteria:
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healthy men
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written consent
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body mass index (BMI) 18.5 - 25
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age 20-50 years
Exclusion Criteria:
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any kind of disease
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regular medication
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aarhus University Hospital | Aarhus | Denmark | 8000 |
Sponsors and Collaborators
- University of Aarhus
Investigators
- Principal Investigator: Jens Otto L. Jørgensen, Professor, Aarhus University / Aarhus University Hospital
- Study Director: Jens Otto L. Jørgensen, Professor, Aarhus University / Aarhus University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Ketone8000