Comparison of albumin excretion rate obtained with different times of collection.

This study was undertaken to assess the usefulness of different techniques for determination of albumin excretion rate (AER). Ninety patients with type I (insulin-dependent) diabetes mellitus and 45 with type II (non-insulin-dependent) diabetes mellitus, with AER/24 h of less than 200 micrograms/min, were included. All patients were free of major systemic complications of diabetes and overt kidney disease (mean serum creatinine 1.1 +/- 0.1 mg/dl, range 0.4-1.2 mg/dl). We compared timed day, night, and 24-h specimens, as well as timed spot specimens during water-induced diuresis. Most patients with type I (75 of 90) and type II (30 of 45) diabetes had AER less than 20 micrograms/min and showed significant differences in AER that were dependent on the collection time. Differences were diminished or absent with AER less than 20 micrograms/min. Sensitivity, specificity, and prediction rates of AER in different specimens were evaluated against 24-h AER. Use of albumin concentrations and albumin-creatinine ratios did not improve test performance in comparison with AER. Sampling time and the overall rate of AER influenced measurement of urinary albumin excretion. Day or 24-h AER is most useful to determine the presence of abnormal AER. AER and albumin concentration in spot samples are of limited use for initial screening and frequently require day or 24-h specimens of AER for confirmation. Day or 24-h AER should be used for long-term follow-up of the diabetic patient.

Intestinal digestion of dipeptides in experimental diabetes in the rat.

Intestinal digestion of two dipeptides, leucyl-leucine and phenylalanyl glycine was studied in vivo in diabetic and control rats utilizing the segmental perfusion technique. Both proximal and distal segments of the small intestine were perfused with 20 mM of each substrate with 140 mM NaCl and 0.5% polyethylene glycol. There was no statistically significant difference in the rates of luminal disappearance (hydrolysis) of the two dipeptides between the control and diabetic animals.

Effect of alloxan-induced diabetes on intestinal peptidases in the rat.

Intestinal transport of amino aicds, similar to sugar absorption, is enhanced in experimental diabetes. Because peptidases play a significant role in peptide digestion, we examined the effect of diabetes on intestinal peptidases. Leucyl-naphthylamidase and leucyl-glycine hydrolase (brush border peptidases) and prolyl-glycine hydrolase (cytosol peptidase) were assayed in the brush border and cytosol fraction in diabetic rats 7 days after alloxan administration. Mucosal weight, protein concentration, and total and specific activity of leucyl-naphthylamidase and leucyl-glycine hydrolase were significantly increased in diabetes in the brush border but not in cytosol fraction. By contrast, prolyl-glycine hydrolasw was not affected in cytosol fraction or brush border. These data indicate that brush border peptidases are increased in experimental diabetes. This adaptive response of the small intestinal mucosa is similar to disaccharidase elevation and alteration in the intestinal absorptive function which occurs in experimental diabetes.

Characterization of p-aminobenzoic acid transport across the rat intestine.

The intestinal absorption of PABA, a member of the vitamin B complex, was characterized in vivo and in vitro in the rat by the segmental intestinal perfusion and everted gut sac technique. Net PABA absorption was directly proportional to substrate concentration, and saturation of absorption did not occur with increasing concentrations of PABA (1 to 50 mM), indicating a nonsaturable process. Jejunal and ileal absorption rates were similar and were not influenced by the presence of glucose or the absence of sodium in the test solution. Similarly, 14C-PABA transport in vitro was nonsaturable and proportional to PABA concentration (0.05, 0.5, 1, 10, and 50 mM). It was not inhibited by ouabain or other PABA analogues such as folic acid and benzoic acid. These studies indicate that PABA, a vitamin B cofactor, is absorbed by a nonsaturable, sodium-independent process, which characterizes passive diffusion and is similar to the absorption of other vitamin B members.

Effect of pancreatic duct ligation on exocrine pancreatic function and structure in the rabbit.

4 weeks after pancreatic duct ligation in the rabbit, fecal and luminal chymotrypsin were detected in concentrations similar to the control group. Pancreatic changes in the ligated group were marked dilatation of the main pancreatic duct, proliferation and distention of ductules and fibrosis. Despite pancreatic duct ligation and fibrosis, proteolytic enzymes continued to secrete into the duodenal lumen. These results suggest that pancreatic duct ligation in the rabbit is not associated with total pancreatic insufficiency.

Intestinal absorptive and digestive function in pernicious anemia.

We examined the digestive and absorptive function of the small intestinal mucosa in three patients with pernicious anemia to determine the functional correlates of the morphologic changes previously described. Digestive brush border enzymes (disaccharidases and leucyl-naphthylamidase) in jejunal biopsy specimens from the patients followed a normal distribution compared with those in the control group. With the exception of one patient with mild steatorrhea, the rest of the absorption test results were within the normal range. Jejunal perfusion studies, however, with glucose, sodium and water showed intestinal secretion of sodium and water, i.e., net movement of sodium and water from plasma to lumen, in the presence of normal glucose absorption. Follow-up studies in two patients after treatment with vitamin B12 did not reveal any significant improvement in the absorption rates from the pretreatment period. This abnormality of sodium and water transport in pernicious anemia represents another intestinal defect of a systemic disease which is not corrected by vitamin B12 replacement therapy.

Lactase deficiency--a comparative study of diagnostic methods.

The diagnostic value of 1-14C-lactose breath test was compared with the standard lactose tolerance test and lactase assay in jejunal biopsies in 16 control subjects, 14 patients with lactase deficiency (LD) proven by lactase assay and 20 patients with irritable bowel syndrome (IBS). 14CO2 specific activity in the 2-hr breath collection after administration of 1-14C-lactose (5 muCi) provided a satisfactory separation between the control and LD group. Values were 7.0 +/- 2.0% dose administered/mmoles 14CO2 X 10(-3) (mean +/- SD) in the control group versus 2.1 +/- 1.5 in LD (P less than 0.001) versus 4.9 +/- 2.3 in IBS (P less than 0.01). 1-14C-lactose breath test was superior to standard lactose tolerance test in specificity (P less than 0.05) and provided a satisfactory correlation between 14C-lactose absorption and lactase assay (r = 0.77). The prevalence of LD in IBS was 40% by the breath test and 35% by lactase assay, suggesting that lactose malabsorption may play a role in the symptoms in the population of some patients with IBS. It appears that 1-14C-lactose breath test is a sensitive, specific and accurate method for the diagnosis of LD in clinical practice and suitable for large scale epidemiological surveys.

Effect of aspirin on intestinal absorption of glucose, sodium, and water in man.

The effect of aspirin on small intestinal function in six healthy volunteers was examined using a segmental perfusion technique, with a test solution of 40 mM D-glucose, 140 mM NaCl, and 0-5% polyethylene glycol. Jejunal glucose, sodium, and water absorption rates were inhibited by 50% after oral administration of 2-6 g aspirin. Adenosine triphosphate (ATP) concentration was assayed in jejunal mucosal biopsies before and after aspirin. There was an almost 50% decrease in mucosal ATP levels after aspirin. This effect may be mediated through cellular injury and impairment of mitochondrial energy metabolism. These data suggest that aspirin may significantly alter small intestinal function. It appears possible that the inhibitory effect of aspirin on glucose absorption may account, at least in part, for the lower blood sugar levels observed with the use of the drug.

Digestion of tripeptides and disaccharides: relationship with brush border hydrolases.

Intestinal digestion of two tripeptides (leucyl-glycyl-glycine, prolyl-glycyl-glycine) and two disacchrarides (sucrose, maltose) was examined in the hamster by intestinal perfusion in vivo and hydrolysis of the substrates by microvillus membranes. Perfusion studies showed that luminal disappearance rates of leucyl-glycl-glycine were significantly higher than prolyl-glycyl-glycine (P less than o.001), sucrose (P less than 0.001), and maltose (P less than 0.005). Hydrolytic products of leucyl-glycyl-glycine, sucrose, and maltose were detected in the gut lumen in appreciable concentrations, whereas negligible concentrations of prolyl-glycyl-glycine products were present. Leucyl-glycyl-glycine hydrolysis in microvillus membranes was markedly higher than prolyl-glycyl-glycine (P less than 0.001), which was predominant in the cytoplasmic fraction. These results indicate that leucyl-glycyl-glycine, like sucrose and maltose, is hydrolyzed at the membrane. With some tripeptides, i.e., leucyl-glycyl-glycine, digestion occurs at the microvillus membrane with subsequent transport of hydrolytic products into the intestinal epithelial cell. Other tripeptides, i.e., prolyl-glycyl-glycine, may cross the membrane and undergo intracellular hydrolysis by cytoplasmic peptidases.