Wednesday, December 10, 2008

Can we preserve muscle wasting in another way?

GH is very expensive. Another way to give growth hormone is to provide an orally based releasing agent. This is an article demonstrating the concept and clinical application.

"Dietary energy restriction induces a predictable catabolic response in normal subjects (4, 5). This loss of nitrogen is associated with a decrease in insulin-like growth factor-I (IGF-I) and an increase in GH (19, 20), suggesting GH resistance. However, the resistance is not absolute, because administration of exogenous GH will effect an increase in IGF-I and increase nitrogen retention (4, 5). Because MK-677 is a potent GH secretagogue, the present study was undertaken to determine whether MK-677 could reverse the catabolic response to dietary energy restriction in healthy volunteers. "


MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism1
M. G. Murphy, L. M. Plunkett, B. J. Gertz, W. He, J. Wittreich, W. M. Polvino2 and D. R. Clemmons
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 2 320-325Copyright © 1998 by The Endocrine Society

The reversal of diet-induced negative nitrogen balance by GH suggests a possible therapeutic role for GH treatment in catabolic patients. A double-blind, randomized, placebo-controlled, two-period, cross-over study was designed to investigate whether MK-677, an orally active nonpeptide mimic of GH-releasing peptide, can reverse diet-induced protein catabolism. Eight healthy volunteers (ages 24–39 yr) were calorically restricted (18 kcal/kg·day) for two 14-day periods. During the last 7 days of each diet period, subjects received either oral MK-677 25 mg or placebo once daily. There was a 14- to 21-day washout interval between periods. During the first week of caloric restriction (i.e. diet alone), daily nitrogen losses were similar for both treatment groups (mean ± SE; MK-677 group -2.67 ± 0.40 g/day vs. placebo group -2.83 ± 0.26 g/day). During the second week (diet and study drug), mean daily nitrogen balance was 0.31 ± 0.21 g/day in the MK-677 treatment group compared with -1.48 ± 0.21 g/day in the placebo group

In conclusion:
MK-677 reverses diet-induced nitrogen wasting, suggesting that if these short-term anabolic effects are maintained in patients who are catabolic because of certain acute or chronic disease states, it may be useful in treating catabolic conditions.

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