AJP - Renal Physiology, Vol 258, Issue 5 1304-F1310, Copyright © 1990 by American Physiological Society
Kinetics of system A amino acid uptake by muscle: effects of insulin and acute uremia
B. J. Maroni, R. W. Haesemeyer, M. H. Kutner and W. E. Mitch
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322.
We found that acute renal failure (ARF) depresses maximal responsiveness to
insulin of system A amino acid transport in muscle [Maroni, Karapanos, and
Mitch. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F74-F80,
1986]. To examine mechanisms for this change, we measured the kinetics of
system A in response to insulin and ARF in epitrochlearis muscle. Insulin
stimulation increased the diffusion constant (KD) approximately twofold in
muscles from both ARF and control rats, suggesting that insulin can
modulate nonsaturable alpha-(methylamino)isobutyrate uptake. Compared with
basal values, insulin did not significantly change maximal transport
velocity (Vmax) in ARF or control rats; however, insulin decreased
Michaelis constant (Km) by 79 and 63%, respectively. Inhibition of protein
synthesis with cycloheximide did not prevent stimulation of system A by
insulin. Acute uremia had no effect on nonsaturable uptake or basal system
A kinetics. However, ARF produced opposing effects on insulin-stimulated
system A kinetics. There was a approximately 47% decrease in Vmax, which
was partially offset by a 66% reduction in Km. In summary, both insulin and
ARF modulate system A kinetics by mechanisms that are independent of
protein synthesis.
