posted May 08, 2000 11:46 PM            

Heres's the abstract from http://endo.edoc.com/jcem/v83n2/362-pdf-frame.html

ABSTRACT
Obesity is associated with blunted GH secretion, unfavorable body
composition, and increased cardiovascular mortality. The objective of
this study was to investigate the effects of oral treatment with the GH
secretagogue MK-677 on GH secretion and body composition in oth-erwise
healthy obese males. The study was randomized, double blind,
parallel, and placebo controlled. Twenty-four obese males, aged
18�50 yr, with body mass indexes greater than 30 kg/m 2 and waist/hip
ratios greater than 0.95, were treated with MK-677 25 mg (n 5 12)
or placebo (n 5 12) daily for 8 weeks.
Serum insulin-like growth factor I (IGF-I) increased approximately
40% with MK-677 treatment (P , 0.001 vs. placebo). Serum IGF-binding
protein-3 was also significantly increased (P # 0.001 vs.
placebo). GH and PRL (peak and area under the curve values) were
significantly increased after the initial dose of MK-677. Significant
increases, with the exception of peak PRL, persisted at 2 and 8 weeks
of treatment. The increases in GH and PRL after the initial dose were
significantly greater than the increase seen after multiple doses.
Serum and urinary concentrations of cortisol were not increased at 2
and 8 weeks (P 5 NS, vs. placebo). Fat-free mass increased signifi-cantly
in the MK-677 treatment group when determined with dual
energy x-ray absorptiometry (P , 0.01) or using a four-compartment
model (P ,0.05). Total and visceral fat were not significantly changed
with active therapy. The basal metabolic rate was significantly in-creased
at 2 weeks of MK-677 treatment (P 5 0.01) but not at 8 weeks
(P 5 0.1). Fasting concentrations of glucose and insulin were un-changed,
whereas an oral glucose tolerance test showed impairment
of glucose homeostasis at 2 and 8 weeks.
Weconclude that 2-month treatment with MK-677 in healthy obese
males caused a sustained increase in serum levels of GH, IGF-I, and
IGF-binding protein-3. The effects on cortisol secretion were tran-sient.
Changes in body composition and energy expenditure were of
an anabolic nature, with a sustained increase in fat-free mass and a
transient increase in basal metabolic rate. Further studies are needed
to evaluate whether a higher dose of MK-677 or a more prolonged
treatment period can promote a reduction in body fat. (J Clin Endo-crinol
Metab 83: 362�369, 1998)

posted May 09, 2000 08:51 PM            

BUMP

------------------
"The days nobody else goes to the gym
are the days you should work the hardest!"

posted May 10, 2000 01:17 AM            

Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK-677.

Svensson J, Carlsson B, Carlsson LM, Jansson JO, Bengtsson BA

Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden.

OBJECTIVE: Growth hormone (GH) treatment decreases total body fat while this effect has not yet been documented for the oral GH secretagogue MK-677. In the present study, the effects of MK-677 treatment on serum levels of leptin, thyroid hormones and testosterone were determined. DESIGN: This was a randomized, double-blind, and parallel study. Twenty-four healthy obese males, 19-49 years of age, with body mass index (BMI) > 30 kg/m2 and a waist:hip ratio > 0.95, were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. RESULTS: MK-677 treatment increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment (P < 0.05 vs. placebo) but no significant change was observed at 8 weeks. An increase in serum free 3, 5, 3'-triiodothyronine (free T3) was not detected until 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Peak serum thyroid stimulating hormone (TSH) concentration after MK-677 administration was similar to that after placebo administration at initiation of treatment and at 2 weeks. At 8 weeks of MK-677 treatment, mean peak serum TSH concentration was increased (P < 0.05 vs. placebo) although it remained within the normal range. Serum peak values of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were similar after MK-677 and placebo administration. MK-677 treatment reduced serum total testosterone (P < 0.05 vs. placebo) although total testosterone/sex hormone-binding globulin (SHBG) ratio (an index of free testosterone) was not changed. CONCLUSION: Treatment with the oral GH secretagogue MK-677 transiently increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment, and increased serum free T3 after 8 weeks. These results indicate that MK-677 treatment is able to affect circulating factors of importance for adipose tissue mass and fuel metabolism.

posted May 10, 2000 01:27 AM            

Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).

Svensson J, Jansson JO, Ottosson M, Johannsson G, Taskinen MR, Wiklund O, Bengtsson BA

Research Center for Endocrinology and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden.

Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.

Publication Types:
Clinical trial
Randomized controlled trial

PMID: 10372705, UI: 99299920
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10372705&dopt=Abstract

posted May 10, 2000 01:30 AM            

Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males.

Svensson J, Ohlsson C, Jansson JO, Murphy G, Wyss D, Krupa D, Cerchio K, Polvino W, Gertz B, Baylink D, Mohan S, Bengtsson BA

Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Goteborg, Sweden.

The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.

Publication Types:
Clinical trial
Randomized controlled trial

PMID: 9661080, UI: 98325521
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9661080&dopt=Abstract

posted May 10, 2000 01:30 AM            

Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.

Copinschi G, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, Mendel CM, De Lepeleire I, Bolognese JA, Van Cauter E

Center for the Study of Biological Rhythms (CERB) and Laboratory of Experimental Medicine, Free University of Brussels, Belgium.

Previous studies have indicated the existence of common mechanisms regulating sleep and somatotropic activity. In the present study, we investigated the effects of prolonged treatment with a novel, orally active, growth hormone secretagogue (MK-677) on sleep quality in healthy young and older adults. Eight young subjects (18-30 years) followed a double-blind, placebo-controlled, three-period crossover design. Each subject participated in three 7-day treatment periods (with bedtime drug administration), presented in random (Latin square) order, and separated by at least 14 days. Doses were 5 and 25 mg MK-677 and matching placebo. Six older subjects, ages 65-71 years, each participated in two 14-day treatment periods (with bedtime drug administration) separated by a 14-day washout. Doses were 2 and 25 mg MK-677 during the first and second periods, respectively. Baseline sleep and hormonal data were obtained on the 2 days preceding the beginning of the first 14-day treatment period. In young subjects, high-dose MK-677 treatment resulted in an approximately 50% increase in the duration of stage IV and in a more than 20% increase in REM sleep as compared to placebo (p < 0.05). The frequency of deviations from normal sleep decreased from 42% under placebo to 8% under high-dose MK-677 (p < 0.03). In older adults, treatment with MK-677 was associated with a nearly 50% increase in REM sleep (p < 0.05) and a decrease in REM latency (p < 0.02). The frequency of deviations from normal sleep also decreased (p < 0.02). The present findings suggest that MK-677 may simultaneously improve sleep quality and correct the relative hyposomatotropism of senescence.

Publication Types:
Clinical trial
Controlled clinical trial

PMID: 9349662, UI: 98007818

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9349662&dopt=Abstract