Effects of glucocorticoids on glutamine metabolism in skeletal muscle

Abstract

The effects of dexamethasone on nitrogen and amino acid metabolism in the dog were studied in order to gain insight into the role of glucocorticoids in accelerated proteolysis and altered metabolism of glutamine in catabolic illnesses. After dexamethasone administration at a dose of 0.44 mg X day-1 X kg-1, nitrogen balance shifted from slightly positive (+0.126 g N X day-1 X kg-1) to markedly negative (-0.278 g N X day-1 X kg-1). This was associated with a 23% fall in total free amino acid nitrogen in skeletal muscle, with 80% of the decline accounted for by a decrease in glutamine. Plasma glutamine concentration decreased by 26%, although total plasma free amino acid nitrogen was unchanged because of a 49% increase in alanine. The alterations in intracellular and circulating levels of glutamine were not accompanied by measurable changes in glutamine synthetase or glutaminase activities in skeletal muscle. Hindquarter amino acid flux measurements demonstrated that the decline in intracellular glutamine concentration was associated with a marked increase in glutamine efflux from skeletal muscle. This occurred in spite of minimal changes in the intracellular/extracellular glutamine gradient. It is concluded that accelerated muscle glutamine release caused by glucocorticoids is a major contributor to the decreased glutamine levels in muscle that occur during critical illnesses.

Effects of laparotomy vs pneumoperitoneum on the hepatic catabolic stress response in ambulatory and stationary settings in pigs

“…The combined effects of stress hormones have been shown to be responsible for the metabolic response to injury, and glucagon is probably more important than any other hormone [27]. Glucagon, cortisol, and catecholamines all exert an effect on the ability of synthesis of urea [3,24,28,34]. Insulin has no direct effect on FHNC but may be capable of directing substrates away from the liver [37].…”

A suplementação de glutamina é benéfica em crianças com doenças graves?

“…Nestas circunstâncias de hiper-metabolismo, há aumento dos hormônios catabólicos (CRH, ACTH, glicocorticóides, catecolaminas), que exacerbam a proteólise e a neoglicogênese 3 , excedendo a capacidade de síntese de glutamina no músculo esquelético e ocasionando a diminuição das reservas e da concentração plasmática. Além disso, acredita-se que, recém-nascidos prematuros com baixo peso ao nascimento, por apresentarem reservas energéticas reduzidas e pouca musculatura esquelética, sejam mais susceptíveis a estados de deficiência de glutamina.…”

Introduction to the Symposium Proceedings

“…Thus, many of the fundamental animal and human studies performed in this last half century failed to quantitate GLN and determine its importance as a quantitative intraorgan nitrogen carrier or an organ-specific fuel [for example, see Felig et al (1969)]. However, when protocols were devised to accurately determine concentrations of GLN in fluids and tissues (Mulhbacher et al 1984, Smith andPanico 1985), the importance of this amino acid in nutritional biochemistry and integrative metabolism began to unfold (Muhlbacher et al 1984).…”