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Changes in intestinal transport of L-amino acid and D-glucose in streptozotocin (STZ)-induced hyperglycemic guinea-pig were examined using brush-border membrane vesicles. The vesicles were prepared from guinea-pigs on days 3, 10, and 21 after intravenous injection of STZ (150 mg/kg body weight), and from control animals injected with sodium citrate buffer (pH 4.5) in the same manner. Blood glucose concentration rose to greater than 300 mg/dl in the hyperglycemic guinea-pigs 24 h after STZ injection, and then remained constant. All vesicles obtained under different conditions showed a similar specific activity of alkaline phosphatase, a marker enzyme of the intestinal brush-border membrane, indicating a similar purity of the membrane vesicles. On day 3, Na(+)-dependent amino acid transport was found to be approx. 30% higher in the hyperglycemic than in the control group, and Na(+)-dependent glucose transport was 35% lower in the hyperglycemic than in the control group. On days 10 and 21, Na(+)-dependent amino acid transport had recovered to the control levels, whereas Na(+)-dependent glucose transport was twice as high as in the hyperglycemic than in the control group. Na(+)-independent amino acid and Na(+)-independent glucose transport showed no difference between the hyperglycemic and control groups after STZ injection. The changes in both Na(+)-dependent amino acid and glucose transport were attributed to significant changes in the Vmax values with no change in the apparent Km values. This study clearly demonstrates that hyperglycemia is associated with reciprocal changes in intestinal transport of amino acid and glucose in its acute phase, suggesting an important pathophysiological regulatory mechanism for absorption of nutrients by control of the numbers of specific carriers.

The amino-acid transport systems have been characterized in brush-border membrane vesicles prepared from guinea-pig small intestine. Uptake of all amino acids tested was measured at the initial velocity for 5 s. L-Proline, alpha-(methylamino)isobutyrate, glycine, L-alanine and L-methionine were transported dependent solely on an Na+ gradient from the outside to the inside of the vesicles, and L-cysteine, L-phenylalanine and L-leucine were transported dependent largely on the Na+ gradient with a small fraction of Na+-independent transport. The transport of L-aspartic acid and L-lysine was independent of the Na+ gradient and L-lysine transport was somewhat inhibited by the presence of cations, including Na+, K+ and Li+. A cross-inhibition study of the uptake of these amino acids in the brush border of guinea-pig intestine revealed the presence of at least three Na+-dependent and three Na+-independent carrier-mediated systems. One Na+-dependent system interacted mainly with imino acid. Another Na+-dependent system interacted with neutral amino acids, while a third system was selective for glycine. One Na+-independent system is for acidic amino acids, another is responsible for neutral amino acids and a third for cationic amino acids. These transport systems of amino acids in guinea-pig small intestine are compared with those in rabbit and mouse intestine.