Substrate Metabolism, Growth Hormone Signaling (GH), and Insulin Sensitivity During GH and Ketone Bodies Infusion

Study Overview
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Brief Summary
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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: Ketone bodies changes the insulin sensitivity and substrate metabolism in human subjects 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.

Official Title
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Substrate Metabolism, Growth Hormone Signaling (GH), and Insulin Sensitivity During GH and Ketone Bodies Infusion

Conditions
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Healthy

Intervention / Treatment
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* Drug: Somatropin
* Other: Ketone bodies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy men written consent body mass index (BMI) 18.5 - 25 age 20-50 years Exclusion Criteria: any kind of disease regular medication

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>12 hours of fasting | |
| Experimental: GH infusion<br>12 hours of fasting | Drug: Somatropin<br>* Somatropin infusion (Genotropin®)<br>|
| Experimental: GH and ketone bodies infusion<br>12 hours of fasting | Drug: Somatropin<br>* Somatropin infusion (Genotropin®)<br>Other: Ketone bodies<br>* ketone bodies infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins in muscle- and fat-tissue. | Change in phosphorylation of target proteins using Western Blotting (WB) | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose metabolism | Change in glucose metabolism assessed by tracer kinetics on every study day. | 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. | 
| Insulin and growth hormone signaling, expressed as CHANGE in messenger ribonucleic acid (mRNA) expression of target genes in muscle- and fat-tissue. | Change in mRNA expression of target genes using Polymerase Chain Reaction (PCR). | 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. | 
| Investigation of the balance in the autonomic nervous system | Heart rate variability (the study of beat-to-beat fluctuations in heart rate). | 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. |