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This study will investigate whether growth hormone is modulated by the enzyme SIRT1 and by that is stimulating lipolysis on expense of IGF-I production. This is done in 10 healthy men on calorie restriction on 4 study days with fat and skeletal muscle biopsies.
It has been shown that calorie restriction enhances the length of life in yeast, worms, fish and rodent. Whether this elongation of life due to calorie restriction can be applied to humans is not known. However, it is a fact that calorie restriction will decrease the risk of developing metabolic disturbances such as diabetes, hypertension and atherosclerosis.
On the molecular level the specific relations are not fully understood. This study will investigate the possible connection between SITR1 and the relation to the GH/IGF-I axis and STAT5b in healthy men. The participant will fast 42 and 12 hours respectively, and have GH or placebo infusions. The design is a classical 2x2 design and will be randomized.
Knowledge of the interactions between calorie restriction, SIRT1, STAT5b and the GH/IGF-I axis will apply important information about the relations between aging, energy metabolism and metabolic disturbances.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 42 hour fast/GH infusion | Experimental |
| |
| 42 hour fast/Placebo infusion | Experimental |
| |
| 12 hour fast/GH infusion | Experimental |
| |
| 12 hour fast/Placebo infusion | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GH hormone infusion | Drug | Norditropin 30 ng/kg/min |
|
| Measure | Description | Time Frame |
|---|---|---|
| Description of intracellular pathways to clarify the interplay between calorie restriction, SIRT1, STATb5, and the GH/IGF-I axis | All study days consists of 3 hour basic periods and 3 hours hyperinsulinemic, euglycemic clamp. | 6 hour study days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jens Otto L Jørgensen, Professor | University Hospital of Aarhus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of Aarhus, Norrebrogade | Aarhus | 8000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31668393 | Derived | Hjelholt AJ, Lee KY, Arlien-Soborg MC, Pedersen SB, Kopchick JJ, Puri V, Jessen N, Jorgensen JOL. Temporal patterns of lipolytic regulators in adipose tissue after acute growth hormone exposure in human subjects: A randomized controlled crossover trial. Mol Metab. 2019 Nov;29:65-75. doi: 10.1016/j.molmet.2019.08.013. Epub 2019 Aug 20. | |
| 24148194 |
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| ID | Term |
|---|---|
| D005215 | Fasting |
| ID | Term |
|---|---|
| D005247 | Feeding Behavior |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D019382 | Human Growth Hormone |
| ID | Term |
|---|---|
| D013006 | Growth Hormone |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
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| 42 hour fast | Behavioral | The participant will be fasting 42 hours prior to the start of the study day, drinking water is allowed |
|
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| 12 hour fast | Behavioral | 12 hour fast will be used as a control scenario to 42 hour fast |
|
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| Nellemann B, Vendelbo MH, Nielsen TS, Bak AM, Hogild M, Pedersen SB, Bienso RS, Pilegaard H, Moller N, Jessen N, Jorgensen JO. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity. Acta Physiol (Oxf). 2014 Feb;210(2):392-402. doi: 10.1111/apha.12183. Epub 2013 Nov 22. |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |