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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | No Intervention | 12 hours of fasting | |
| GH infusion | Experimental | 12 hours of fasting |
|
| GH and ketone bodies infusion | Experimental | 12 hours of fasting |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Somatropin | Drug | Somatropin infusion (Genotropin®) |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jens Otto L. Jørgensen, Professor | Aarhus University / Aarhus University Hospital | Principal Investigator |
| Jens Otto L. Jørgensen, Professor | Aarhus University / Aarhus University Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Aarhus | 8000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36240323 | Derived | Hogild ML, Hjelholt AJ, Hansen J, Pedersen SB, Moller N, Wojtaszewski JFP, Johannsen M, Jessen N, Jorgensen JOL. Ketone Body Infusion Abrogates Growth Hormone-Induced Lipolysis and Insulin Resistance. J Clin Endocrinol Metab. 2023 Feb 15;108(3):653-664. doi: 10.1210/clinem/dgac595. |
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| ID | Term |
|---|---|
| D019382 | Human Growth Hormone |
| D007657 | Ketone Bodies |
| ID | Term |
|---|---|
| D013006 | Growth Hormone |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
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| Ketone bodies | Other | ketone bodies infusion |
|
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. |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D007659 | Ketones |
| D009930 | Organic Chemicals |