Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects
| Autor: | M Farmer, Michael O. Thorner, M A Bach, E. Van Cauter, Johannes D. Veldhuis, Emily H. Skiles, Suzan S. Pezzoli, G J Gormley, K Y Cole, L M Schilling, A M Taylor, D A Krupa, Ian Chapman, Mark L. Hartman |
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| Rok vydání: | 1996 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Indoles Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Administration Oral Stimulation Peptide hormone Placebo Biochemistry Insulin-like growth factor Endocrinology Double-Blind Method Oral administration Internal medicine medicine Humans Spiro Compounds Insulin-Like Growth Factor I Aged Hydrocortisone Aged 80 and over Dose-Response Relationship Drug business.industry Insulin Biochemistry (medical) Middle Aged Somatropin Growth Hormone Female business medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 81:4249-4257 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.81.12.8954023 |
| Popis: | Aging is associated with declining activity of the GH axis, possibly contributing to adverse body composition changes and increased incidence of cardiovascular disease. The stimulatory effects on the GH-insulin-like growth factor I (IGF-I) axis of orally administered MK-677, a GH-releasing peptide mimetic, were investigated. Thirty-two healthy subjects (15 women and 17 men, aged 64-81 yr) were enrolled in a randomized, double blind, placebo-controlled trial. They received placebo or 2, 10, or 25 mg MK-677, orally, once daily for 2 separate study periods of 14 and 28 days. At baseline and on day 14 of each study period, blood was collected every 20 min for 24 h to measure GH, PRL, and cortisol. Attributes of pulsatile GH release were assessed by 3 independent algorithms. MK-677 administration for 2 weeks increased GH concentrations in a dose-dependent manner, with 25 mg/day increasing mean 24-h GH concentration 97 +/- 23% (mean +/- SE; P0.05 vs. baseline). This increase was due to an enhancement of preexisting pulsatile GH secretion. GH pulse height and interpulse nadir concentrations increased significantly without significant changes in the number of pulses. With 25 mg/day MK-677 treatment, mean serum IGF-I concentrations increased into the normal range for young adults (141 +/- 21 microgram/L at baseline, 219 +/- 21 micrograms/L at 2 weeks, and 265 +/- 29 micrograms/L at 4 weeks; P0.05). MK-677 produced significant increases in fasting glucose (5.4 +/- 0.3 to 6.8 +/- 0.4 mmol/L at 4 weeks; P0.01 vs. baseline) and IGF-binding protein-3. Circulating cortisol concentrations did not change, and PRL concentrations increased 23%, but remained within the normal range. Once daily treatment of older people with oral MK-677 for up to 4 weeks enhanced pulsatile GH release, significantly increased serum GH and IGF-I concentrations, and, at a dose of 25 mg/day, restored serum IGF-I concentrations to those of young adults. |
| Databáze: | OpenAIRE |
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