Metabolism, Insulin Resistance, Hypopituitarism
Conditions
Keywords
ghrelin, metabolism, type 2 diabetes, insulin resistance
Brief summary
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.
Detailed description
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.
Interventions
DRUGAcipimox
Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day
DRUGGhrelin
Ghrelin infusion 4.2 ng/kg/min throughout the investigation day
OTHERPlacebo
placebo tablets or saline infusion
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* males with hypopituitarism in regard to growth hormone and ACTH in stabile treatment regime * age 18-65 * BMI 20-35
Exclusion criteria
* abuse of alcohol * malign disease * medication other than that expected for hypopituitarism * known disease other than hypopituitarism * participation in isotope investigations the last 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of ghrelin during basal and hyperinsulinemic conditions | 5 hours investigation day | 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. |
Countries
Denmark
Outcome results
None listed