Characteristics of L-glutamine transport in the perfused rat exocrine pancreas: lack of sensitivity to insulin and streptozotocin-induced experimental diabetes.

The transport specificity of L-glutamine influx in the perfused rat exocrine pancreas has been investigated using a dual isotope tracer dilution technique. During a single circulation through the isolated pancreas, an epithelial uptake of 71 +/- 1% (n = 10) was measured for L-(3H)glutamine relative to the extracellular marker D-(14C)mannitol. L-(3H)glutamine uptake was markedly inhibited during perfusion with 10 mM L-glutamine, L-histidine, L-methionine, L-serine, or L-cysteine. The system A--specific analogue alpha-methylaminoisobutryic acid and L-glutamic acid were ineffective inhibitors. L-Glutamine transport was saturable (0.05 - 32 mM), with an apparent Kt = 14 +/- 1 mM and Vmax = 13.4 +/- 0.7 mumol/min g (n = 6), and largely insensitive to perfusion with 1 mM ouabain or a sodium-free solution. In kinetic inhibition experiments, the Vmax/Kt ratio for L-glutamine remained unaltered during perfusion with 10 mM L-serine, whereas L-glutamine appeared to inhibit L-serine transport noncompetitively. Tracer L-glutamine efflux was enhanced by increasing concentrations of unlabeled L-glutamine and 10 mM L-serine. Similarly, tracer L-serine efflux was accelerated in the presence of 10 mM L-glutamine. Unlike L-serine, the transport activity for L-glutamine was not stimulated by 100 microU/ml exogenous insulin or streptozotocin-induced experimental diabetes. These findings suggest that in the exocrine pancreas, L-glutamine transport is mediated primarily by a large neutral system L.