Healthy
Conditions
Keywords
men
Brief summary
Glucagon has been used for decades as a test of growth hormone (GH) reserve. The pathway by which GH is stimulated by glucagon is not established. Acyl ghrelin has been shown to increase GH levels and to be stimulated by an increase in adrenergic activity. The proposed study will test the concept that with the fall in blood glucose it is likely that there is a sympathetic discharge which contributes to the increase in acyl ghrelin and indirectly leads to the increase in GH and cortisol.
Detailed description
Glucagon given to healthy adults in doses of 1-1.5 mg i.m. has been shown to result in a peak glucagon level in the circulation after 30 min, followed by an increase in glucose and insulin levels. The subsequent decline in glucose, insulin and glucagon was followed by an increase in cortisol and GH. Ghrelin is a 28 amino acid peptide which is released from the fundus of the stomach, within the oxyntic glands and the small intestine. It circulates in two major forms, acylated and des-acylated ghrelin. Acylated ghrelin has strong GH-releasing effects which are mediated via the G-protein coupled ghrelin receptor. The proposed study will test the concept that with the fall in blood glucose during a glucagon test it is likely that there is a sympathetic discharge which contributes to the increase in acyl ghrelin and indirectly leads to the increase in GH and cortisol.
Interventions
DRUGAtenolol
Beta-1 receptor antagonist
DRUGSaline
Saline s.c.
DRUGGlucagon
Glucagon s.c.
DRUGPlacebo
Sugar Pill
Sponsors
Novo Nordisk A/S
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy normal men 2. Age 18-30 yrs 3. BMI 18-27 kg/m2
Exclusion criteria
1. Medication or previous surgery known to affect ghrelin secretion. 2. Medications known to have an impact on body weight (Seroquel, tricyclic antidepressants). 3. Medications known to have an impact on the beta adrenergic system. 4. Coronary artery disease, congestive heart failure, peripheral vascular disease, diabetes mellitus, significant hypertension (BP \>180 systolic or \>100 diastolic at rest); renal, hepatic, pulmonary disease; untreated hypothyroidism, untreated hyperthyroidism; history of seizure disorder; history of malignancy (other than some skin cancers), history of active chronic infections (e.g., HIV, tuberculosis). 5. Endocrine disorders, i.e., pheochromocytoma, adrenal insufficiency 6. Hematocrit \< 41% men 7. History of daily tobacco use within past 3 months 8. Chronic alcohol abuse by history 9. Weight not stable (more than 10% weight change or more over past 6 months) 10. Strenuous exercise for average of more than 60 min/day 11. Investigational drug within past 6 weeks 12. Psychiatric history especially eating disorders 13. Transmeridian travel within 2 weeks prior to or during study 14. Known hypersensitivity to beta-blockers 15. Estimated Glomerular Filtration Rate below 60 mL/min/1.73m2. 16. Known cardiac dysrhythmia, especially first degree heart block. -
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Circulating acyl-ghrelin concentration after glucagon stimulation with and without beta-adrenergic blockade | 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Association between circulating acyl-ghrelin concentration and GH and cortisol after glucagon administration with and without beta-adrenergic blockade | 18 months |
Countries
United States
Contacts
Primary ContactRalf Nass, MD
Outcome results
None listed