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: 1. Ketone bodies changes the insulin sensitivity and substrate metabolism in human subjects 2. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
10
Somatropin infusion (Genotropin®)
ketone bodies infusion
Aarhus University Hospital
Aarhus, Denmark
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)
Time frame: 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
Glucose metabolism
Change in glucose metabolism assessed by tracer kinetics on every study day.
Time frame: 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).
Time frame: 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).
Time frame: 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.
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