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This study will investigate the non-growth-hormone-dependent metabolic effects of the hormone Ghrelin in growth hormone deficient subjects by examining the insulin tolerance as well as signal proteins in fat and muscle biopsies.
Ghrelin is a relatively 'new' hormone that is produced in the stomach and to a lesser extend in the hypothalamus of the brain. The actions of ghrelin are diverse and includes stimulation of the appetite center of the brain and the release of growth hormone. We have for the first time shown that ghrelin also stimulates the metabolism of fatty acids and induces insulin resistance in skeletal muscle. These effects have we confirmed in growth hormone deficient subjects on a stabile substitution treatment with growth hormone and hydrocortisone. With these subjects we can investigate the effects of ghrelin that are independent of growth hormone. The present study is a continuation of these findings, as we wish to investigate whether the insulin resistance effect of ghrelin is dependent of the concomitant metabolism of fatty acids. This is possible by administration of the niacin acid antagonist Acipimox, that blocks the fatty acid metabolism reversibly. We have applied this experimental principle in other settings with success.
Knowledge of the effects of ghrelin in general can in shot-sight as well as in long-sight have great importance for the understanding of growth disorders from overweight and type 2 diabetes to malnutrition and eating disorders.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ghrelin / Acipimox | Active Comparator | Ghrelin infusion and tablet acipimox |
|
| Ghrelin / placebo | Active Comparator | Ghrelin infusion and placebo tablets |
|
| Placebo / Acipimox | Active Comparator | saline infusion and tablet Acipimox |
|
| Placebo / placebo | Placebo Comparator | saline infusion and placebo tablets |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acipimox | Drug | Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effects of ghrelin during basal and hyperinsulinemic conditions | Growth hormone deficient patient investigated with ghrelin infusion and pharmacological antilipolysis (Acipimox) in a randomized cross-over study with 4 study days. During each visit signal proteins in muscle and fat biopsies are investigated with PCR, wester blot and activity assays for ghrelin, growth hormone and insulin. Further is glucose metabolism investigated in basal conditions and during hyperinsulinemic euglycemic clamp. | 5 hours investigation day |
| Effects of ghrelin during basal and hyperinsulinemic conditions | Effects of ghrelin on heart rate variability | 5 hours investigation day |
| Effects of ghrelin during basal and hyperinsulinemic conditions | Effects of ghrelin on thirst, fluid intake, urine production and natriuresis | 5 hours investigation day |
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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 | Aarhus | 8000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31608930 | Derived | Jepsen SL, Vestergaard ET, Larraufie P, Gribble FM, Reimann F, Jorgensen JOL, Holst JJ, Kuhre RE. Ghrelin Does Not Directly Stimulate Secretion of Glucagon-like Peptide-1. J Clin Endocrinol Metab. 2020 Jan 1;105(1):266-75. doi: 10.1210/clinem/dgz046. | |
| 28736944 | Derived | Vestergaard ET, Cichosz SL, Moller N, Jorgensen JOL, Fleischer J. Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation. Br J Clin Pharmacol. 2017 Dec;83(12):2671-2677. doi: 10.1111/bcp.13384. Epub 2017 Aug 24. |
| Label | URL |
|---|---|
| Original publication on the results from the study | View source |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D007018 | Hypopituitarism |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C027696 | acipimox |
| D054439 | Ghrelin |
| ID | Term |
|---|---|
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
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| Ghrelin | Drug | Ghrelin infusion 4.2 ng/kg/min throughout the investigation day |
|
| Placebo | Other | placebo tablets or saline infusion |
|
|
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
| D003920 | Diabetes Mellitus |
| D000602 | Amino Acids, Peptides, and Proteins |