Up-regulation of liver system A for neutral amino acid transport in euglycemic hyperinsulinemic rats.
To determine the role of insulin on the in vivo modulation of liver system A activity, we used the euglycemic hyperinsulinemic clamp coupled to the measurement of solute uptakes into plasma membrane vesicles partially purified from livers of hyperinsulinemic rats and their saline-infused controls. The clamp was performed in chronically catheterized rats, either in the fasted state, 24 h after surgery (Group I), or after 3 days of recovery (Group II). System A activity, measured as the MeAIB-inhibitable L-alanine uptake, was selectively induced by hyperinsulinemia, although the effect was much greater in Group II than in Group I rats (137% vs. 24% over the basal values, respectively). This might be explained by the higher basal levels found in those liver plasma membrane vesicles from Group I fasted animals. Hyperinsulinemia also decreased blood amino acids but to a similar extent in both experimental groups. This suggests that amino acid depletion by itself may not cause up-regulation of system A. Other transport activities involved in neutral amino acid transport (Systems ASC, N and L) were not modified by the clamp. The induction of system A cannot be explained by changes in the dissipation rate of the Na+ transmembrane gradient, because the differences between insulin- and saline-infused rats remained even when the electrochemical Na+ gradient was disrupted in the presence of monensin. Thus, hyperinsulinemia might induce an increase in the number of transporters inserted into the plasma membrane.
Ferrer-Martínez
A
A
Departament de Bioquímica i Fisiologia, Universitat de Barcelona, Spain.
Casado
J
J
Leturque
A
A
Felipe
A
A
Pastor-Anglada
M
M
D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015309:Glucose Clamp Technique; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008985:Monensin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D002352:Carrier Proteins; D007328:Insulin; D008985:Monensin