Alanyl-glutamine prevents muscle atrophy and glutamine synthetase induction by glucocorticoids
| Autor: | I. E. Karl, D. F. Osborne, L. E. Wegrzyn, R. C. Hickson |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Physiology Rats Sprague-Dawley Atrophy Glutamate-Ammonia Ligase Physiology (medical) Glutamine synthetase Internal medicine medicine Animals RNA Messenger Muscle Skeletal Glucocorticoids Hydrocortisone Alanine biology Body Weight Skeletal muscle Dipeptides Organ Size medicine.disease Muscle atrophy Enzyme assay Rats Glutamine Muscular Atrophy medicine.anatomical_structure Endocrinology Enzyme Induction Muscle Fibers Fast-Twitch biology.protein Female medicine.symptom Glucocorticoid medicine.drug |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 271:R1165-R1172 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.1996.271.5.r1165 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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