Intestinal transport of glucose and amino acids in experimental uremia.

Abstract

Summary: The effects of chronic uremia on the intestinal transport of amino acids and glucose were assessed by an in vivo perfusion technique in young uremic rats and pair-fed controls. The experimental rats were rendered uremic by a modification of the conventional nephrectomy, and control animals were sham operated. All intestinal perfusions were performed 4 to 6 wk after completion of surgical induction of uremia. The mean BUN of the experimental group at the time of evaluation of intestinal transport was 79 ± 18 mg/dl (mean ± S.E.) compared to 23 ± 9 mg/dl (P < 0.02) in control animals. A 20-cm-long segment of proximal jejunum was perfused in vivo with Krebs-Henseleit buffers containing amino acids and carbohydrates with 14C-and 3H-labeled tracers. The jejunal absorption of tyrosine was significantly increased in uremic rats: 5.63 ± 0.42 as compared to 3.47 ± 0.28 nmoles/min cm in the controls (P < 0.001). Similarly, the absorption of phenylalanine was increased in the uremic rats; 5.79 ± 0.41 versus 3.74 ± 0.32 nmoles/min cm in the control rats (P < 0.001). Confirmation that increased phenylalanine absorption represented a true lumen-to-blood flow was obtained by measurement of [3H]phenylalanine in blood drawn from the aorta after 60 min of perfusion. The blood count in uremic rats was 2,307 ± 257 dpm/ml versus 1173 ± 172 dpm/ml in controls (P < 0.01). The absorption of glucose along the jejunum was also increased in the uremic rats over the controls both at 4 and 40 mM. At 4 mM, the absorption in uremic rats was 27.79 ± 1.84 versus 21.02 ± 1.66 nmoles/min cm (P < 0.01) in controls. At 40 mM, the values were 228.5 ± 16.3 and 170.9 ± 16.9 nmoles/min cm, respectively (P < 0.02). In contrast, the absorption of histidine and alpha-aminoisobutyric acid was not significantly different between uremic and control animals. The alterations in jejunal transport were associated with a decreased incorporation of [3H]phenylalanine into protein in the cell membrane-rich portion of intestinal mucosal scrapings (43.7 ± 4.7 nCi/g protein versus 94.2 ± 13.1 nCi/g protein in controls; P < 0.01). There was also secretion of glucose from blood-to-intestinal lumen, which was significantly greater in uremic than in control animals: 1.41 ± 0.16 versus 0.87 ± 0.05 nmoles/min cm (P < 0.01). These results are consistent with an alteration of the integrity of the jejunal mucosa in uremia which affects its permeability and alters the transport of nutrient. Speculation: The decreased incorporation of phenylalanine into membrane-bound material of the jejunal mucosa and the increased blood-to-lumen flux of glucose in uremic rats may indicate a defect in the integrity of the intestinal mucosa. This may be associated with an altered premeability, which facilitates increased intestinal absorption of solutes. These kinds of changes in uremia seem to be different in pathogenesis from those induced by malnutrition per se. The observed changes in jejunal absorption appear to compensate for, rather than to contribute to, the malnutrition and growth failure typical of chronic uremia.