Alanyl-glutamine prevents muscle atrophy and glutamine synthetase induction by glucocorticoids. Hickson, R. C., L. E. Wegrzyn, D. F. Osborne, and I. E. Karl. School of Kinesiology, University of Illinois at Chicago, Chicago, IL 60608-1516 and Department of Internal Medicine, Metabolism Division, Washington University School of Medicine, St Louis, MO 63110
APStracts 3:0148R, 1996.
The aims of this work were to establish whether glutamine infusion via alanyl-glutamine dipeptide provides effective therapy against muscle atrophy from glucocorticoids; and whether the glucocorticoid induction of glutamine synthetase (GS) is downregulated by dipeptide supplementation. Rats were given hydrocortisone 21-acetate or the dosing vehicle and were infused with alanyl-alanine (AA) or alanyl -glutamine (AG) at the same concentrations and rates (1.15 umol.min -1.100g BW-1, 0.75 ml/h) for 7 days. When compared to AA infusion in hormone-treated animals, AG infusion prevented total body and fast -twitch muscle mass losses by over 70%. Glucocorticoid treatment did not reduce muscle glutamine levels. Higher serum glutamine was found in the AG-infused (1.72 0.28 umol/ml) as compared to the AA infused group (1.32 0.06 umol/ml), but muscle glutamine concentrations were not elevated by AG infusion. Following glucocorticoid injections, GS enzyme activity was increased by 2-3-fold in plantaris, fast-twitch white (superficial quadriceps), and fast-twitch red (deep quadriceps) muscle/fiber types of the AA group. Similarly GS mRNA was elevated by 3.3-4.1-fold in these same muscles of hormone-treated, AA-infused rats. AG infusion diminished glucocorticoid effects on GS enzyme activity to 52-65% and on GS mRNA to 31-37% of the values with AA infusion. These results provide firsthand evidence of atrophy prevention from a catabolic state using glutamine in dipeptide form. Despite higher serum and muscle alanine levels with AA infusion than with AG infusion, alanine alone is not a sufficient stimulus to counteract muscle atrophy. The AG-induced muscle sparing is accompanied by diminished expression of a glucocorticoid-inducible gene in skeletal muscle. However, glutamine regulation of GS appears complex and may involve more regulators than muscle glutamine concentration alone. 

Received 20 October 1995; accepted in final form 2 April 1996.
APS Manuscript Number R658-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96