# EXERCISE AND MUSCLE ATROPHY PREVENTION

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 1992 · $202,052

## Abstract

In humans and animals, exercise and other forms of increased contractile
activity are known to inhibit the muscle wasting associated with
diseases and experimental conditions resulting from glucocorticoid
excess. Recent evidence also indicates that preserving muscle glutamine
concentration has the potential to serve as another therapeutic
deterrent to muscle atrophy. By examining hormone-responsive, up-
regulated (glutamine synthetase, GS) and down-regulated (myosin heavy
chains) genes as models for understanding protein regulation, the long-
term objectives are to elucidate the molecular events by which exercise
and glutamine therapy prevents atrophy from this state. The first
overall goal (aims one and two) is: to determine whether maintaining
muscle glutamine concentration by glutamine supplementation prevents
muscle wasting from glucocorticoids; to evaluate whether glutamine
regulates glutamine synthetase expression at a posttranslational level;
To determine whether preserving muscle glutamine concentration
interferes with the glucocorticoid-mediated depression of myosin heavy
chain synthesis; and to examine whether the combination of exercise and
glutamine therapy can produce additive effect in atrophy prevention. A
second research goal (aims three and four) is directed at examining
whether alpha-ketoglutarate supplementation prevents atrophy through
maintenance of muscle glutamine levels; whether alpha-ketoglutarate can
antagonize hormone-mediated changes in glutamine synthetase expression
and in myosin heavy chain synthesis; and whether the combination of
glutamine and alpha-ketoglutarate supplementation are essential for
optimally preserving muscle glutamine and in protecting against-atrophy.
Results from the present grant period have shown that increased
contractile activity diminishes basal and glucorticoid-induced GS enzyme
activity and mRNA content. Consequently, using transgenic animals, a
third goal (aim five) will determine whether the endurance training
effects on GS are: (a) indicative of a generalized glucocorticoid
response in muscle; (b) director at promoter elements on the GS gene;
and (c) directed at an activating transcription factor/cyclic AMP-
response element enhancer region of the gene.

This project will establish the extent of the individual and combined
contributions of glutamine, alpha-ketoglutarate, and exercise in
producing optimal therapeutic conditions against atrophy. These results
will further establish the importance of GS in the regulation of muscle
mass and the mechanism of its gene regulation by exercise. New basic
knowledge can be obtained into the reported anabolic effects of
glutamine on protein synthesis and the relationship of these alterations
with preservation of muscle mass. An understanding of the mechanisms
associated with this type of atrophy and atrophy prevention can provide
the basis for therapy as well as in identifying the mechanisms
underlying other types of muscle wasting conditions and d...

## Key facts

- **NIH application ID:** 3159559
- **Project number:** 2R01AR039496-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **SAM.gov UEI:** W8XEAJDKMXH3
- **Principal Investigator:** ROBERT C HICKSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $202,052
- **Award type:** 2
- **Project period:** 1989-04-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159559

## Citation

> US National Institutes of Health, RePORTER application 3159559, EXERCISE AND MUSCLE ATROPHY PREVENTION (2R01AR039496-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159559. Licensed CC0.

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