AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 5 1165-R1172, Copyright © 1996 by American Physiological Society
Alanyl-glutamine prevents muscle atrophy and glutamine synthetase induction by glucocorticoids
R. C. Hickson, L. E. Wegrzyn, D. F. Osborne and I. E. Karl
School of Kinesiology, University of Illinois at Chicago 60608-1516, USA.
The aims of this work were to establish whether glutamine infusion via
alanyl-glutamine dipeptide provides effective therapy against muscle
atrophy from glucorticoids 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 alanine (AA) or alanyl-glutamine (AG) at the same
concentrations and rates (1.15 mumol.min-1.100 g body wt-1, 0.75 ml/h) for
7 days. Compared with 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 mumol/ml)
compared with the AA-infused group (1.32 +/- 0.06 mumol/ml), but muscle
glutamine concentrations were not elevated by AG infusion. Following
glucocorticoid injections, GS enzyme activity was increased by two- to
threefold 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- to 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.
