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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
9
Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.
Placebo is administered 4 times previous to and during the investigation day.
GH substitution as usually
GH substitution pause two days prior to the experimental day
University Hospital of Aarhus
Aarhus, Denmark
Lipolytic activity measured as area under the curve (AUC) for FFA (free fatty acid) before and during clamp-conditions.
Time frame: 1 year
GH signaling proteins and gene targets in adipose and skeletal muscle tissues measured by western blotting and qPCR
Time frame: 1,5 years
Insulin sensitivity as measured by M value and GIR (glucose infusion rate)
Time frame: 6 months
Substrate metabolism as measured by indirect calorimetry, tritiated glucose and circulating hormones and metabolites
Time frame: 1 year
PDH (pyruvate dehydrogenase) activity in skeletal muscle measured by an PDH activity assay
Time frame: 1 year
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