Hypopituitarism, Insulin Resistance, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Diseases, Pituitary Diseases, Brain Diseases
Conditions
Brief summary
Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric restriction GH predominantly promotes fat metabolism. GH counteracts the effect of insulin in many tissues, of which insulin-stimulated glucose uptake in skeletal muscle has been most extensively studied. Substrate competition between elevated free fatty acids and glucose is suggested as a mechanism, and this hypothesis can be tested mechanistically by means of acipimox, which is a nicotinic acid that suppresses the fat metabolizing effects of GH. The hypothesis is, that the suppressive effect of GH on insulin-stimulated glucose uptake in skeletal muscle is obviated by acipimox-induced inhibition of fat metabolism. In order to investigate this, eight adult hypopituitary patients with documented GH-deficiency will be studied in the presence and absence of GH and acipimox, respectively, and biopsies from skeletal muscle and subcutaneous adipose tissue will be analyzed. Knowledge of the effects of growth hormone and fat metabolism 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
Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.
DRUGPlacebo
Placebo is administered 4 times previous to and during the investigation day.
DRUGGH substitution
GH substitution as usually
OTHERGH pause
GH substitution pause two days prior to the experimental day
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* hypopituitary patients with documented GH-deficiency
Exclusion criteria
* other significant disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Lipolytic activity measured as area under the curve (AUC) for FFA (free fatty acid) before and during clamp-conditions. | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| GH signaling proteins and gene targets in adipose and skeletal muscle tissues measured by western blotting and qPCR | 1,5 years |
| Insulin sensitivity as measured by M value and GIR (glucose infusion rate) | 6 months |
| Substrate metabolism as measured by indirect calorimetry, tritiated glucose and circulating hormones and metabolites | 1 year |
| PDH (pyruvate dehydrogenase) activity in skeletal muscle measured by an PDH activity assay | 1 year |
Countries
Denmark
Outcome results
None listed