Stimulation of jejunal mucosal protein synthesis by luminal glucose. Effects with luminal and vascular leucine in fed and fasted rats.

This study was conducted to determine whether short-term (1.75 h) luminal glucose perfusion increases the mucosal protein synthesis rate in rat small intestine. A luminal perfusate containing 56 mM glucose was compared with a control perfusate containing mannitol in two jejunal segments constructed in the same animal. Mucosal protein synthesis rates were determined when the tracer amino acid was administered intravenously and intraluminally. The results indicated that luminal glucose perfusion rapidly stimulated mucosal protein synthesis in the fed state by 20% and 37% with the labeled amino acid derived from the vascular and luminal compartment, respectively. A 16-h fast abolished the stimulatory effect of glucose when the labeled amino acid was given intravascularly but not intraluminally. These effects of glucose could be ascribed to a direct alteration of mucosal metabolism rather than to indirect systemic effects.

Ammonia production from intraluminal amino acids in canine jejunum.

Dietary protein increases the blood ammonia concentration when hepatic metabolic function is impaired, but the site of ammonia production and its specific precursors have not been clearly defined. The purpose of this study is to determine if individual luminal amino acids are metabolized to ammonia by the jejunum during the process of absorption. In anesthetized, fasted dogs, a cannula was inserted into the mesenteric vein draining a segment of the jejunum weighing approximately 18 g, and the ends of the segment were ligated to isolate its blood flow. Ammonia and amino acids were determined in luminal fluid as well as arterial and mesenteric venous blood. One of six amino acids (10 mM) was luminally perfused for a 15-min equilibration period and two 15-min collection periods, and the results were compared with control periods that preceded and followed the amino acid perfusion. Alanine, leucine, and glutamine significantly (P less than 0.01) increased ammonia release into mesenteric venous blood by 37, 42, and 106%, respectively, whereas threonine, serine, and glycine had no effect. Net jejunal uptake of glutamine from arterial blood, which accounts for ammonia release by the jejunum in the basal state, was not altered by perfusions other than with glutamine. Luminal glycine perfusion also caused an increased release of serine into mesenteric venous blood and alanine perfusion increased the release of glutamate. Glutamine perfusion caused increased release of glutamate, alanine, proline, and citrulline. These results indicate that some, but not all, luminal amino acids are partially metabolized to ammonia during the process of absorption in the small intestine.

Nitrogen in fecal bacterial, fiber, and soluble fractions of patients with cirrhosis: effects of lactulose and lactulose plus neomycin.

To determine how lactulose and lactulose plus neomycin might alter nitrogen metabolism in the colon we investigated the effect of these agents on the distribution of nitrogen in the bacterial, soluble, and fiber fractions of stool. The alterations in fecal nitrogen excretion were additionally correlated with changes in total body urea synthesis and degradation rates. Six patients with stable cirrhosis received a control diet alone followed by the administration of lactulose (56 +/- 6 gm/day), and eight similar patients received lactulose alone (63 +/- 5 gm/day) followed by the addition of neomycin (4 gm/day). Their feces were partitioned into individual fractions by physical separation. Lactulose administration increased nitrogen excreted in the bacterial fraction by 165% (from 0.52 +/- 0.14 gm/day to 1.38 +/- 0.21 gm/day) and by 135% in the soluble fraction (from 0.58 +/- 0.08 gm/day to 1.36 +/- 0.23 gm/day). When lactulose was supplemented with neomycin, the nitrogen content of the bacterial fraction decreased by 28%. Lactulose caused a 23% reduction in the urea production rate that was mainly accounted for by increase in fecal nitrogen excretion. The addition of neomycin caused a further reduction in urea production that was explained by an inhibition of urea degradation. These results demonstrate that a major effect of lactulose was to augment the incorporation of nitrogen into fecal bacteria although nitrogen in the soluble fraction also increased. The additional nitrogen excreted in the fecal bacterial and soluble fractions caused a reduction in urea synthesis.

Effects of vegetable diets on nitrogen metabolism in cirrhotic subjects.

This study compared the effect of a vegetable diet with an animal protein diet on various aspects of nitrogen metabolism to identify what components of the vegetable diet might be causing beneficial therapeutic effects in hepatic encephalopathy. Vegetable diets contained 4.5-fold greater amounts of fiber (56 +/- 3 g/day) and reduced amounts of methionine, tyrosine, and tryptophan. In 6 stable cirrhotic subjects without encephalopathy, vegetable diets caused a significant reduction in the urea production rate from 106 +/- 5 to 89 +/- 5 mg X kg-1 X 24 h-1 of urea nitrogen. This was mainly accounted for by a fall in urinary urea output. Vegetable diets also caused a fall in total urinary nitrogen, which was accounted for by the fall in urea nitrogen, and a comparable increase in fecal nitrogen from 12 +/- 2 to 28 +/- 5 mg X kg-1 X 24 h-1. The fecal bacterial fraction contained 63% of the increase in stool nitrogen. Most plasma amino acids, including methionine, tyrosine, phenylalanine, as well as total and free tryptophan, were unchanged. The effect of vegetable diets on nitrogen metabolism can be mainly accounted for by the increased intake of dietary fiber and increased incorporation and elimination of nitrogen in fecal bacteria.

Effects of lactulose and neomycin on urea metabolism in cirrhotic subjects.

In our previous studies of cirrhotic subjects lactulose caused a 25% decrease in the urea production rate associated with a decrease in urinary urea excretion and an increase in stool nitrogen. The decrease in the rate of urea production was an indirect measure of reduction in gut ammonia production. The present study was designed to determined if the poorly adsorbed antibiotic neomycin had an additive effect in reducing ammonia production when administered in combination with lactulose. Six stable cirrhotic subjects received isonitrogenous diets during separate lactulose and lactulose + neomycin treatment periods. The addition of neomycin to a lactulose regimen caused a 17% reduction in the urea production rate that was quantitatively accounted for by a 70% reduction in the urea degradation rate. The intestinal urea clearance rate demonstrated a parallel reduction, indicating an inhibition of bacterial ureolysis. There was no evidence that neomycin altered the effects of lactulose since urinary urea excretion did not rise, fecal nitrogen remained high, and stools remained acidic. These results demonstrate that neomycin inhibited bacterial ureolysis when administered with lactulose while lactulose itself was metabolized and its individual effect on nitrogen metabolism persisted. Lactulose and neomycin, when administered together, had an additive effect in reducing gut ammonia production in cirrhotic subjects.

Comparative effects of lactulose and magnesium sulfate on urea metabolism and nitrogen excretion in cirrhotic subjects.

In previous studies with cirrhotic subjects administration of oral lactulose caused a reduction in the urea production rate associated with an increase in fecal nitrogen excretion. The change in urea production rate in response to lactulose therapy was an indirect measure of a reduction in total gut ammonia production. In this study, the effect of magnesium sulfate administration was compared with lactulose therapy in 5 cirrhotic subjects to determine whether the effects of lactulose on nitrogen metabolism might be attributed to a nonspecific, cathartic effect. Both magnesium sulfate (5-15 g/day) and lactulose (40-80 g/day) caused significant and comparable increases in stool weight, solids, and total nitrogen. Only lactulose caused a reduction in fecal pH. Magnesium sulfate had no significant effect on the urea production rate or urinary nitrogen excretion, whereas lactulose caused a 25% reduction in the urea production rate and an 18% reduction in urinary nitrogen excretion. The latter was accounted for by a fall in urinary urea. Nitrogen balance was more negative during magnesium sulfate than during control or lactulose periods since magnesium sulfate increased fecal nitrogen without altering urinary nitrogen excretion. These data demonstrated that the effects of lactulose on nitrogen excretion and urea metabolism were not duplicated by equivalent cathartic doses of magnesium sulfate.