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Acetic acid suppresses the increase in disaccharidase activity that occurs during culture of caco-2 cells.

To understand how blood glucose level is lowered by oral administration of vinegar, we examined effects of acetic acid on glucose transport and disaccharidase activity in Caco-2 cells. Cells were cultured for 15 d in a medium containing 5 mmol/L of acetic acid. This chronic treatment did not affect cell growth or viability, and furthermore, apoptotic cell death was not observed. Glucose transport, evaluated with a nonmetabolizable substrate, 3-O-methyl glucose, also was not affected. However, the increase of sucrase activity observed in control cells (no acetic acid) was significantly suppressed by acetic acid (P < 0.01). Acetic acid suppressed sucrase activity in concentration- and time-dependent manners. Similar treatments (5 mmol/L and 15 d) with other organic acids such as citric, succinic, L-maric, L-lactic, L-tartaric and itaconic acids, did not suppress the increase in sucrase activity. Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme, whereas the activities of other hydrolases (alkaline phosphatase, aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected. To understand mechanisms underlying the suppression of disaccharidase activity by acetic acid, Northern and Western analyses of the sucrase-isomaltase complex were performed. Acetic acid did not affect the de novo synthesis of this complex at either the transcriptional or translational levels. The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity. This suppression seems to occur during the post-translational processing.

Acetic Acid↗

Disaccharidase activities and intestinal absorption in infants with congenital intestinal obstruction.

The results of studies on disaccharidase activities and on intestinal absorption in cases of complete and incomplete congenital small bowel obstruction are presented. Assays of the activities of maltase, isomaltase, sucrase, trehalase, and lactase have been performed on biopsy specimens taken at the time of surgery. In specimens taken from above the site of obstruction, the activities are reduced for all disaccharidases, and are particularly low for trehalase and lactase. There was no difference between the cases with complete and incomplete obstruction. Distal to a complete obstruction, trehalase and lactase were reduced, whereas in cases of incomplete obstruction, the activities of all disaccharidases were within what is considered normal in the reference material. Two months after surgery, the disaccharidase activities were found to be normal. One month after surgery, the absorption of glucose and vitamin A was markedly impaired in cases with complete obstruction, whereas that of D-xylose was not significantly reduced from normal. In cases with incomplete obstruction, the results did not differ from those found in normal infants. The fact that failure to thrive is common during the first months after birth in patients with congenital intestinal atresia, even when surgery is successful, may be explained by deficient intestinal absorption, particularly in patients with complete obstruction.

Body Weight↗

Histologic findings are not correlated with disaccharidase activities in infants with protracted diarrhea.

Histologic assessment as well as information about the disaccharidase activity of the small intestinal mucosa can be useful in the management of patients with small intestinal mucosal damage. In an effort to determine whether the degree of small intestinal mucosal damage would be reflected in a corresponding reduction in disaccharidase activity, we compared small intestinal mucosal histology with the results of disaccharidase activity measured in per oral suction small intestinal biopsies obtained from 21 infants with protracted diarrhea. The degree of small intestinal mucosal damage was graded using a subjective score (i.e., 0 to 4+ damage) by a pathologist (P) and by a computer-assisted digitizing system (to assess villus surface area, VSA, and villus/crypt ratio, V/C) in a blinded fashion. The mean (+/- SD) age of the infants was 2.5 +/- 1.5 months, and the duration of diarrhea was 25.2 +/- 11.5 days. There was good correlation between the results obtained from the digitizing system and from the pathologist: VSA versus P, r = 0.695; V/C versus P, r = 0.791; p = 0.0004. All infants demonstrated some degree of small intestinal mucosal damage. The mean (+/- SD) values for P, VSA, and V/C were 2.2 +/- 1.3, 2.9 +/- 0.9, and 0.9 +/- 0.5, respectively. The mean values for lactase, sucrase, and maltase were 17.1 +/- 17.0, 71.1 +/- 54.0, and 224.3 +/- 233 mumol/min/g protein, respectively. No correlation was observed between the histologic scoring results and lactase, sucrase, or maltase measurements. Expressing the disaccharidase activities per unit wet weight of tissue did not improve the correlations. Log transformation of the data also failed to improve the correlations.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Enteral insulin-like growth factor-I augments intestinal disaccharidase activity in piglets receiving total parenteral nutrition.

BACKGROUND: Partial enteral nutrition is administered to infants on parenteral nutrition to stimulate intestinal function. Herein, the hypothesis that supplementation of partial enteral nutrition with insulin-like growth factor-I would augment intestinal development was investigated. METHODS: One-day-old piglets (n = 29) were randomly assigned to five dietary treatment groups: 100% of energy as enteral formula, 100% of energy as total parenteral nutrition, or 80% parenteral nutrition/20% enteral formula supplemented with either 0, 0.2, or 1 mg/kg insulin-like growth factor-I for 7 days. Weight gain, intestinal weight, morphology, protein, and DNA content and disaccharidase activity and mRNA expression were assessed. RESULTS: Parenterally fed piglets had similar whole body weight gain and serum hormone concentrations but reduced intestinal mucosal weight, villus height, and sucrase and lactase activity compared with 100% enterally fed pigs. Partial enteral nutrition alone increased mucosal weight and protein content, villus height, and disaccharidase activity compared with 100% parenterally fed piglets. No effect of the lower dose of insulin-like growth factor-I (0.2 mg/kg per day) was observed, but supplementing partial enteral nutrition with 1 mg insulin-like growth factor-I/kg further increased villus width and cross-sectional area and disaccharidase activity compared with partial enteral nutrition alone. Lactase mRNA expression was not affected by insulin-like growth factor-I, suggesting that the primary site of regulation of lactase by insulin-like growth factor-I occurs after transcription. CONCLUSIONS: Enteral insulin-like growth factor-I augmented intestinal morphology and disaccharidase activity in parenterally fed piglets over that observed with partial enteral nutrition alone. Thus enteral insulin-like growth factor-I may represent an efficacious clinical adjunct to promote intestinal development of parenterally fed neonates.

Animals↗

Intestinal disaccharidase activity following pancreatic duct occlusion in the rat.

The influence of pancreatic secretions on growth and brush-border enzyme activity, throughout the entire small intestine, was examined in the rat. Pancreatic secretions were excluded from the gut lumen by stapling the pancreatic ducts, without interruption of bile flow. The entire small intestine was studied as four segments; the duodenum and three distal segments of equal length. Weight of intestine and mucosa, and mucosal sucrase, isomaltase, lactase, and alkaline phosphatase activity were measured 10-15 days following pancreatic duct occlusion, or sham-operation. The duodenum of pancreatic duct-occluded animals exhibited significant hypertrophy. In general, specific and total disaccharidase activities were greater in duct-occluded animals than in controls throughout the intestine. The increase was more pronounced in distal than in proximal segments. The sucrase/isomaltase ratio was significantly greater in pancreatic duct-occluded animals than in controls in the two distal segments. Alkaline phosphatase activity was not affected by pancreatic duct occlusion. The greater relative increase of disaccharidase activities and sucrase/isomaltase activity ratios in the distal segments of duct-occluded animals, indicates a more important regulatory role of pancreatic enzymes in the distal small intestine. It is concluded that regulation of intestinal brush-border enzyme activity by pancreatic secretion is selective for enzyme and site as follows: disaccharidases, but not alkaline phosphatase, are regulated; the sucrase subunit of the sucrase/isomaltase complex is most sensitive to regulation, while lactase is least sensitive; and the regulatory effect on disaccharidases is greater in distal than in proximal intestine.

Animals↗

Delayed disaccharidase development in a rabbit model of intrauterine growth retardation.

Intrauterine growth retardation (IUGR) affects almost 10% of infants born in the United States. It may be responsible for delayed gastrointestinal function and is an important cause of perinatal morbidity and mortality. The New Zealand White rabbit provides an optimal model for the study of naturally occurring IUGR. At term, birth weight is determined by fetal position within the bicornuate uterus. The small intestinal disaccharidase enzymes are indicators of bowel maturity and function. To examine potential differences in disaccharidase development between normal and IUGR fetuses, this rabbit model was investigated. Jejunum was harvested at multiple stages in rabbit development including the third trimester fetus, neonate, and adult. Lactase, maltase, and sucrase enzyme activity, as well as total protein content, was determined. Results were analyzed by the 2-tailed t test and ANOVA. Lactase activity appeared in the mid-third trimester, peaked in the early neonatal period, then declined to adult levels. Maltase activity appeared in the early third trimester and gradually rose to adult levels. Sucrase remained at trace levels until the mid-neonatal period, reaching adult levels by weaning. Both lactase and maltase activity were depressed in IUGR fetuses compared with their normal littermates. This pattern of disaccharidase depression continued into the neonatal period until catch-up growth occurred at 2 wk when levels equalized. This report describes differential small intestinal disaccharidase development between normal and growth-retarded rabbit fetuses in a naturally occurring model of IUGR.

Animals↗

Induction of chick embryonic intestinal disaccharidases by hydrocortisone and sucrose in the organ culture system.

The effect of hydrocortisone and sucrose on the development of chick intestinal disaccharidases was studied using the organ culture system. When intestines of 15- and 17-day-old embryos were cultured in the presence of hydrocortisone, there was significant enhancement of disaccharidases activity compared with the control. However, there was no effect in the 20-day embryonic intestines. On the other hand, the disaccharidase activity of cultured intestines from 20-day-old chick embryos were significantly stimulated by the addition of sucrose. The observed increase in disaccharidase activity induced by the administration of hydrocortisone in 17-day-old embryos in vitro was sensitive to actinomycin D and cycloheximide. The activity induced by the administration of sucrose in 20-day-old embryos in vitro was sensitive to cycloheximide but insensitive to actinomycin D.

Animals↗

Human intestinal disaccharidase activities: correlations with age, biopsy technique, and degree of villus atrophy.

The relationship between intestinal morphology, disaccharidase activity, and disaccharide absorption is controversial. A retrospective study of 798 consecutive biopsies was performed to determine whether disaccharidase activities varied by subject age, biopsy technique, and degree of villus atrophy. Lactase activity was inversely correlated with age in the absence or presence of villus atrophy; sucrase, maltase, and palatinase activities did not correlate with age. Biopsies obtained by capsule or endoscopy had similar disaccharidase activities. In subjects 24 months of age or younger, the degree of mucosal injury was inversely correlated with lactase activity. In subjects older than 24 months, the degree of mucosal injury was inversely correlated with maltase and, to a lesser extent, lactase activities. The data suggest that disaccharidase activities in mucosal biopsies, whether obtained by endoscopy or capsule, are diminished in the presence of mucosal injury and correlate inversely with the degree of injury.

Adolescent↗

Does zinc deficiency affect intestinal protein content or disaccharidase activity?

Zinc deficiency has been associated with impared carbohydrate absorption in patients with intestinal disease; however, it is not known whether the carbohydrate malabsorption is caused by the zinc abnormality. Because zinc is needed for protein synthesis, we investigated the effect of zinc deficiency on the total and specific activities of the intestinal glycoprotein disaccharidases. We found that zinc deficiency impairs total body growth and causes marked reductions in intestinal mucosal protein content and disaccharidase activity. However, the protein content and disaccharidase activities were reduced to a similar degree, and both were proportional to the final total body weight. We also found zinc deficiency to have no effect on intestinal villus height or crypt depth. We conclude that zinc deficiency inhibits somatic growth but does not disproportionately affect intestinal mucosal protein content, disaccharidase activity, or intestinal architecture.

Animals↗

[Rat intestinal disaccharidases during cyclophosphamide treatment (author's transl)].

Rat intestinal disaccharidase activities were investigated during treatment with different doses of 2-[bis-(2-chlorethyl)-amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide (cyclophosphamide). In all experiments, disaccharidase activities decreased--although not too drastically--within 2--3 days after beginning treatment. Loss of activity was not reversed during the period of experimentation. Contrary to previous investigations, cyclophosphamide did not exert direct toxic effects on intestinal disaccharidases. Decrease of intestinal disaccharidase activities can be interpreted to be due to cyclophosphamide effects on the proliferation cycle of epithelial crypt cells resulting in a decreased number of full-function cells.

Animals↗

Small bowel biopsy for disaccharidase levels: evidence that endoscopic forceps biopsy can replace the Crosby capsule.

Lactase, sucrase and maltase activities in endoscopic biopsies from the second part of the duodenum were compared to those in Crosby capsule biopsies from the proximal jejunum. In patients with villous atrophy disaccharidase activities were reduced compared with histologically normal mucosa in the duodenum and jejunum. Disaccharidase activities were significantly lower in the duodenum than in the proximal jejunum of patients with histologically normal mucosa and in those with partial villous atrophy but not significantly different for total villous atrophy patients. Primary and secondary disaccharidase deficiencies can be identified in biopsies from the duodenum. Duodenal biopsy is a valid alternative to jejunal biopsy for the diagnosis of disaccharidase deficiency.

Atrophy↗

Intestinal disaccharidases in malnourished infant rats.

In infants suffering from protein-calorie malnutrition, the decreased intestinal mucosal lactase specific activity could be due either to the protein-calorie malnutrition or to the commonly associated enteritis (viral or bacterial) and intestinal parasites. We studied intestinal mucosal disaccharidase (lactase, sucrase, and maltase) specific activity in suckling (1 and 2 wk old), weanling (3 wk old), and postweaning (4 and 6 wk old) control and growth-retarded (malnourished) rats. Growth retardation was induced by feeding mother rats and postweaning rats a diet deficient in protein. In the malnourished rats, with few exceptions, specific activity of the disaccharidases in the intestinal mucosa were similar to those in the corresponding control groups of rats. However, because of marked mucosal atrophy total intestinal mucosal disaccharidase activities were more than 50% lower in the malnourished rats. These findings suggest that the specific activity of the intestinal mucosal disaccharidases is not affected by malnutrition per se.

Animals↗

Disaccharidase levels in the small intestine in patients with diarrhoea following vagotomy and pyloroplasty.

Diarrhoea is a common sequel to vagotomy and pyloroplasty but its cause is unknown. One of our patients who developed this complication had an abnormal lactose barium meal and responded well to a lactose-free diet. This led us to make a systematic study of disaccharidase activity in the small intestine in patients with diarrhoea following vagotomy and pyloroplasty. The small-intestinal disaccharidases have been estimated in jejunal biopsy specimens taken from 23 patients suffering from persistent diarrhoea, either continuous or episodic, after vagotomy and pyloroplasty. The disaccharidase values were normal in all but one of these patients. This patient showed hypolactasia but the sucrase and maltase levels were normal. The jejunal biopsy specimen taken from this patient showed a convoluted pattern under the dissecting microscope and severe partial villous atrophy under the light microscope. A repeat jejunal biopsy taken 20 cm beyond the duodeno-jejunal flexure showed similar appearances and also had a low level of lactase. However, two lactose tolerance tests and a lactose barium meal yielded normal results, suggesting that the low level of lactase in the upper jejunum was not a limiting factor in lactose absorption. The finding of one example of a low lactase level among 23 postvagotomy patients corresponds with what is being found in a study of normal subjects at present in progress. In effect, almost all patients with persistent diarrhoea after vagotomy and pyloroplasty have normal small-intestinal disaccharidase activity.

Adult↗

Butyric acid modulates activities of intestinal and renal disaccharidases in experimentally induced diabetic rats.

To elucidate the effect of feeding of butyric acid on disaccharidase activities, the specific activities of the disaccharidases were measured in the intestinal mucosa and kidney cortex of control and diabetic rats. Diabetes was induced in rats using streptozotocin. Rats were fed with basal diet containing wheat bran (5%) as a source of insoluble dietary fiber and guar gum (2.5%) as a source of soluble dietary fiber. The experimental group received butyric acid at 250, 500 and 750 mg/kg body weight/day. Increased activities of intestinal maltase, sucrase and lactase in diabetic rats were significantly reduced in fiber-fed diabetic group. Supplementation of butyric acid at 500 mg/kg body weight/day showed a further decrease in their activities. The activity of disaccharidases in renal tissue was decreased in diabetic rats and was significantly improved in fiber-fed diabetic group. Butyric acid feeding at 500 mg/kg body weight/day showed further improvement in their activities.

Animals↗

Neural isolation of the jejunoileum. Effect on tissue morphometry, mucosal disaccharidase activity, and tissue peptide content.

The aim of this study was to determine the effects of a model of intestinal extrinsic denervation on mucosal structure and function. Six dogs underwent in situ neural isolation of the jejunoileum (Group 2); six other dogs served as operated controls (Group 1), and five nonoperated dogs were naive controls (Group 3). Thirty-centimeter segments of proximal jejunum and distal ileum were excised before (time zero) and at 2 weeks and 8 weeks postoperatively in Groups 1 and 2, while similar regions were removed at time zero in Group 3. Tissues were analyzed for morphology with quantitative morphometry, mucosal disaccharidase activities (sucrase, maltase, and lactase), and tissue content of selected regulatory peptides in transmural, mucosa/submucosa, and muscularis regions. In situ neural isolation had no significant or consistent effects on morphology/morphometry or on mucosal disaccharidase activities. Tissue content of neuropeptide Y decreased markedly (P < 0.002) in all layers of the jejunal and ileal walls, but tissue content of vasoactive inhibitory polypeptide, substance P, cholecystokinin, neurotensin, met-enkephalin, neurokinin A, somatostatin, and calcitonin gene-related peptide demonstrated only minor changes. The physiologic effects of intestinal transplantation (extrinsic denervation and disruption of intrinsic, enteric neural continuity, and lymphatic drainage) have little effect on morphology, mucosal disaccharidase activity, and tissue content of most regulatory peptides. How these minor alterations might affect enteric function, however, needs to be investigated.

Animals↗

[Intestinal disaccharidase and alkaline phosphatase activities of jejunal biopsies in small bowel diseases of children (author's transl)].

Intestinal disaccharidase activities were determined in 294 jejunal biopsies obtained from 254 children with various disorders of the small bowel, and alkaline phosphatase activity was measured in 251 biopsies. In normal mucosa a broad range of enzyme activity was found corresponding with the data in the literature. A primary disaccharidase deficiency was observed in 5 children with congenital sucrase-isomaltase deficiency and in a 12-year-old Egyptian boy with acquired lactase deficiency. A secondary generalized depression of disaccharidase activity and a diminution of alkaline phosphatase activity existed chiefly in patients who had severe or moderate mucosal damage, also in active coeliac disease and during gluten loading, in protracted diarrhoea of infancy, chronic malabsorption of unknown origin and agammaglobulinemia. During remissions enzyme activities recovered together with mucosal improvement. Low levels of enzyme activities were also seen in some cases of protracted diarrhoea of infancy and chronic malabsorption of unknown origin although only mild mucosal lesions were demonstrated.

Agammaglobulinemia↗

Is the assay of disaccharidase activity in small bowel mucosal biopsy relevant for clinical gastroenterologists?

In a retrospective study, jejunal mucosal disaccharidase and alkaline phosphatase activities have been investigated in 40 controls and patients with proven celiac sprue (n = 26), lactase deficiency (n = 26), osteoporosis or osteomalacia (n = 16), chronic pancreatitis (n = 12), giardiasis (n = 7), or Crohn's disease (n = 7). Apart from a nonselective reduction of mucosal enzyme activities in the sprue syndrome and a selective reduction of lactase activity in the patients with primary lactase deficiency, assays of mucosal disaccharidases revealed only inconstant or slight deviations from the control group and were not of diagnostic significance for any of the above-mentioned disorders. Isolated forms of enzyme deficiencies other than lactase deficiency, such as sucrase-isomaltase or trehalase deficiency were not present among 168 investigations carried out from 1972-1982. It is concluded that assay of small intestinal disaccharidase or alkaline phosphatase activities does not expand the diagnostic impact of morphological examination of small bowel biopsy specimens and modern noninvasive methods for the detection of carbohydrate malabsorption. Thus, the method does not appear a necessary or relevant investigation in routine clinical practice.

Adolescent↗

Developmental patterns of intestinal disaccharidases in human amniotic fluid.

A close relationship exists between relative disaccharidase activities (maltase, sucrase, trehalase, palatinase, turanase, lactase, and cellobiase) in amniotic fluid and corresponding jejunal mucosa of five human fetuses (16 to 21 weeks of gestation) suggesting that these intestinal enzymes pass into amniotic fluid. Serial determination of disaccharidase activities in amniotic fluid samples collected between 10 and 42 weeks of gestation showed maximum mean activities at 14 to 17 weeks of gestation and a rapid drop to less than 12 per cent maximum values at about 22 weeks. This drop is probably caused by combined effects of decreased extrusion rate of intestinal disaccharidases and increased reabsorption of the enzymes in swallowed amniotic fluid with fetal development.

Amniotic Fluid↗