Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The levels of the brush-border enzymes sucrase (sucrose glucohydrolase, EC 3.2.1.48), isomaltase (oligo-1,6-glucosidase, EC 3.2.1.10), maltases 2 and 3 (glucoamylase, EC 3.2.1.3), lactase (beta-galactosidase, EC 3.2.1.23) and trehalase (EC 3.2.1.28) and adsorbed pancreatic alpha-amylase (EC 3.2.1.1) have been measured at twenty-one positions along the small intestines of eighty-four pigs of different ages ranging from 3 weeks to 4.5 years. The state of dilation of the intestine at the sampling points was noted. 2. The levels of sucrase and isomaltase increased with age throughout the age-range studied. Trehalase and the glucoamylases increased with age up to 200--300 d of age. Lactase decreased with age over the whole age range. 3. For the pigs above 10 weeks of age, the distribution pattern of the brush-border enzymes along the intestine did not change with age. Each enzyme had a characteristic distribution curve, with low values at the proximal and distal ends and a peak which was proximal in the instance of lactase and trehalase and approximately mid-way along the gut with sucrase, isomaltase and the glucoamylases. 4. The pattern of distribution of the brush-border enzymes altered with age in the piglets, but approached the adult pattern by 8 weeks. 5. Piglets weaned at 3 weeks had higher levels of sucrase, isomaltase and glucoamylases at 5 weeks than piglets left on the sow. At 8 weeks of age the piglets weaned at 3 weeks still had higher sucrase and isomaltase levels than those on the sow. 6. There was a very close correlation between the sucrase and isomaltase levels, and between the maltase 2 and maltase 3 levels in all the samples, and a fairly close correlation between all these four enzymes. 7. The level of alpha-amylase increased with age but showed no regular distribution pattern, its irregular fluctuations being related to the presence or absence of dilation of the intestine at the time of slaughter rather than to the position along the intestine.
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PMID:The level of distribution of carbohydrases in the small intestine mucosa of pigs from 3 weeks of age to maturity. 696 56

A method of producing semichronic diarrhea is presented. It has been shown that, when fed a combination diet of 50% lactose and 50% commercially available feed, rats are subjected to continuous diarrhea, which lasts for 96 hr or more. The relative lack of the enzyme lactase in the rat results in the accumulation of lactose in the gut and probably by an osmotic effect, sets up conditions for the passage of a watery diarrhea. Various combinations of lactose and commercially available feed were tried and it was observed that rats function without any ill effects (e.g., body-weight loss) and produce consistent watery diarrhea with the above-mentioned combination.
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PMID:A semichronic diarrheal model. 709 93

The in vitro and in vivo production of hydrogen gas (H2) from various carbohydrates or proteins has been examined in normal rats and in rats infected with the nematode Nippostrongylus brasiliensis. Normal rat fecal homogenates were capable of producing H2 in vitro from glucose, sucrose, xylose, lactulose, bovine serum albumin, or casein hydrolysate. Direct injection of glucose, sucrose, xylose, lactulose, bovine serum albumin, or casein hydrolysate into the cecum of normal rats resulted in approximately twice as much H2 production in vivo than when these same carbohydrates or proteins were administered to the normal rats by gavage. Partial small intestinal villous atrophy was produced by infecting rats with the nematode N. brasiliensis. Impaired small intestinal cell function and evidence of malabsorption in the nematode-infected rats included: (a) decreased activity of intestinal cell lactase (-43%), sucrase (-33%), and alkaline phosphatase (-46%); (b) decreased gut sac uptake of 3-O-(methyl-3H]-D-glucose (-21%) or 1-[carboxyl-14C]-aminocyclopentane-1-carboxylic acid (-28%); and (c) increased (+ 64%-561%) 14CO2 production after D-[U-14C]xylose administration. These rats produced approximately twice as much H2 after gavage administration of glucose, sucrose, xylose, bovine serum albumin, or casein hydrolysate compared with normal rats. The present study suggests that H2 analysis may be useful in the evaluation of small intestinal malabsorption states in rats.
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PMID:Use of hydrogen gas (H2) analysis to assess intestinal absorption. Studies in normal rats and in rats infected with the nematode, Nippostrongylus brasiliensis. 728 87

The present study examined the effects of dexamethasone on mucosal adaptation after massive small bowel resection. Rats underwent 80% jejunoileal resection or a sham operation and received either vehicle or 128 micrograms.kg-1.day-1 sc dexamethasone for 7 days. Dexamethasone infusion resulted in decreased weight, DNA content, and protein content in the duodenojejunal and ileal mucosa in both sham and resected rats. Sucrase, lactase, and maltase activities (all in mumol.g protein-1.min-1) in the duodenojejunal mucosa were elevated by dexamethasone infusion. By contrast, enzyme activities were elevated only in the ileal mucosa of dexamethasone-infused sham-operated rats compared with sham-operated control rats, and dexamethasone did not elevate enzyme activities in resected rats. We further examined whether the inhibitory effects of dexamethasone on mucosal adaptation may be related to changes in either insulin-like growth factor (IGF) or IGF binding protein (BP) serum levels. Serum IGF-I and IGF-II levels were markedly decreased in dexamethasone-infused resected and sham-operated rats. IGF BP-1 serum levels were elevated by dexamethasone treatment with a concomitant depression in serum IGF BP-2 levels. IGF BP-3 levels were lowered by dexamethasone treatment in sham-operated rats and by gut resection, and serum IGF BP-4 levels did not change. These results suggest that the growth-inhibiting effects of dexamethasone in small intestinal mucosa may be partially mediated by decreased serum IGF levels or by alterations in IGF activity associated with changes in serum levels of IGF BPs.
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PMID:Dexamethasone inhibits mucosal adaptation after small bowel resection. 751 28

Enterocytes are the major epithelial cell type of the small intestine. Their capacity to secret, absorb and digest specific ions and nutrients is dependent on their position along the length of the small intestine as well as their stage of development as they migrate and differentiate along the crypt-villus axis. In order to further understand the molecular processes that regulate enterocyte differentiation and function, this study has compared the levels of six mRNA species produced by genes expressed in rabbit enterocytes; specifically, the multidrug resistance (MDR1) gene encoding the 170-kDa P-glycoprotein, CaBP 9k, which encodes a putative intracellular calcium buffer, calbindin, LPH, APN, and AP which encode the brush-border hydrolases lactase-phlorizin hydrolase, aminopeptidase N and alkaline phosphatase, respectively, and SGLT1, encoding the brush border Na(+)-glucose cotransporter. The level of each mRNA species has been mapped along the small intestine using quantitative in situ hybridisation. This has revealed characteristic regional variations in the abundance of each of the mRNAs, supporting the opinion that there is a strong genetic component to the maintenance of gradients in epithelial function along the length of the small intestine. Analysis of the cellular accumulation of mRNA during enterocyte migration along the crypt-villus axis, over gut-associated lymphoid tissue, and at epithelial boundaries, has, by contrast, established a clear correlation in the expression of these genes. These data illustrate the dynamics of enterocyte gene expression, thereby providing an insight into the molecular mechanisms which co-ordinate the events of cell transformation that underlie functional differences between the epithelial populations of the small intestine.
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PMID:Parallel patterns of cell-specific gene expression during enterocyte differentiation and maturation in the small intestine of the rabbit. 758 2

Biliopancreatic bypass (BPB), the exclusion of a duodenojejunal loop from the digestive continuity, has been proposed as a bariatric procedure for treatment of morbid obesity. The present study in rats investigated the effect of this surgical procedure on the mucosae of the ileum directly anastomosed to the stomach, and of the jejunum irrigated only by biliopancreatic secretions. The proximal part of the ileum adapted by two-fold increases in its mucosal mass, total protein and RNA content; DNA content was four-fold higher than in sham-operated animals. There was a correlated increase of mucosal enzyme content, except for lactase. In the distal ileal mucosae, a slight, transient augmentation of mucosal mass, protein, DNA and RNA content was observed which tended to compensate for the shortening of the functional gut. No morphological changes were found in the excluded loop, probably because of an endoluminal stimulation by biliopancreatic secretions. Thus, in BPB, biliopancreatic secretions seem to exert trophic effects on the intestinal mucosa, but they are less potent than the endoluminal nutrition that restores the oral-aboral mucosal gradient.
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PMID:Trophic and enzymatic adaptation of the intestine to biliopancreatic bypass in the rat. 769 35

The longitudinal expression of two brush-border enzymes, lactase-phlorizin hydrolase (EC 3.2.1.23/62) and aminopeptidase N (EC 3.4.11.2), was studied in the small intestine of the post-weaned pig. Whereas the level of mRNA, encoding aminopeptidase N (relative to that of beta-actin), only varied moderately from the duodenum to the terminal ileum, the amount of lactase-phlorizin hydrolase mRNA exhibited a sharp maximum in the proximal jejunum. For both enzymes, the level of protein synthesis, studied in cultured mucosal explants, correlated well with the level of mRNA, and no major variation in post-translational processing or intracellular transport was observed along the intestine. The mRNA/specific-activity ratio for both enzymes was markedly (3-5-fold) higher in the duodenum and proximal jejunum, compared with the ileum. This indicates an increased proximal turnover rate, most likely caused by the presence in the gut lumen of pancreatic proteases. In neonatal animals, the level of mRNA for lactase-phlorizin hydrolase in both proximal and distal regions of the intestine was of the same magnitude as in the proximal jejunum of the post-weaned pigs. Our results point to two mechanisms that affect the expression of lactase-phlorizin hydrolase in the pig during development: (1) a primary regulation at the level of mRNA (predominantly in the ileum); (2) an increased rate of turnover of the enzyme, mainly in the duodenum and proximal jejunum, and most likely due to an increased secretion into the gut lumen of pancreatic proteases (a mechanism also affecting aminopeptidase N and probably other brush-border enzymes as well).
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PMID:Lactase-phlorizin hydrolase and aminopeptidase N are differentially regulated in the small intestine of the pig. 810 80

Human lactase-phlorizin hydrolase (LPH), a brush border membrane hydrolase of the small intestine, is synthesized as a precursor molecule that undergoes proteolytic cleavage to yield mature LPH (LPHbeta) by a trypsin-like protease (Naim et al., 1987, 1991). Arg868-Ala869 has been previously proposed to be the putative cleavage site for this processing step. Site-directed mutagenesis of this monobasic site does not lead to the generation of an uncleaved proLPH species, which strongly suggests the existence of an additional cleavage site. Further analyses of LPH synthesized in different cell lines lend support to this hypothesis. Biosynthetic labeling of human intestinal biopsy samples in the presence of trypsin reveals an LPHbeta species that is slightly smaller than the intracellularly cleaved molecule. When the proLPH molecule is screened for potential cleavage sites, two dibasic pairs are revealed upstream of the N-terminal end of brush border LPH at Lys851-Arg852 and Arg830-Lys831. Treatment of proLPH with trypsin for different periods of time supports the idea of at least two cleavage steps, whereby Arg868-Ala869 represents the final cleavage site that generates LPHbeta. We propose that the initial cleavage of proLPH takes place intracellularly at a site further away from Arg868-Ala869, to generate LPHbeta initial; LPHbeta is subsequently cleaved extracellularly in the gut lumen, presumably by trypsin, at Arg868-Ala869 to mature brush border LPH (LPHbeta initial).
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PMID:Maturation of human intestinal lactase-phlorizin hydrolase: generation of the brush border form of the enzyme involves at least two proteolytic cleavage steps. 866 96

The aims of the present study were (a) to maintain the structure and function of the small intestine of the piglet after weaning, and (b) to compare the capacity in vivo of sucking and weaned piglets to digest oral boluses of lactose and sucrose and absorb their monosaccharide products. Piglets were fed on cows' whole milk ad libitum every 2 h for 5 d after weaning. Physiological doses of lactose plus fructose (treatment LAC+FRU) and sucrose plus galactose (treatment SUC+GAL) were administered on day 27 of lactation and on the fifth day after weaning, after which time piglets were killed. Villus height and crypt depth were maintained (P > 0.05) by feeding cows' milk after weaning. The areas under the curves (AUC) for galactose and glucose, adjusted for live weight and plasma volume, increased (P < 0.05) after weaning. Despite the enhancement of gut function after weaning, the galactose index (GalI:AUC for galactose ingested as lactose divided by the AUC for the same dose of galactose ingested as the monosaccharide) and fructose index (FruI: AUC for fructose ingested as sucrose divided by the AUC for the same dose of fructose ingested as the monosaccharide), which are indices of digestive and absorptive efficiency, both decreased after weaning. This apparent anomaly may be reconciled by increased growth, and hence surface area, of the small intestine between weaning and slaughter such that 'total' digestion and absorption most probably increased despite apparent decreases in GalI and FruI. Positive correlations (P < 0.05) between villus height and GalI are consistent with the maximum activity of lactase occurring more apically along the villus. Significant linear relationships (P < 0.05) were recorded between villus height at the proximal jejunum and adjusted AUC for galactose and glucose following treatment LAC+FRU, and between villus height at the proximal jejunum and adjusted glucose AUC following treatment SUC+GAL. These relationships suggest that maximum digestion and absorption occurs at increasing distances along the crypt:villus axis in the weaned pig.
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PMID:Maintenance of villus height and crypt depth, and enhancement of disaccharide digestion and monosaccharide absorption, in piglets fed on cows' whole milk after weaning. 888 13

In previous experiments we showed that intestinal development was dependent upon epithelial-mesenchymal cell interactions. The aim of this study was to investigate the possible role of retinoic acid (RA), a morphogenetic and differentiating agent, on the gut epithelial-mesenchymal unit. For this purpose we first analyzed the effects of a physiological dose of RA on 14-day fetal rat intestine using short-term organ culture experiments, or long-term grafts under the skin of nude mice. In these conditions, RA accelerated villus outgrowth and epithelial cell differentiation as assessed by the onset of lactase expression, and it also stimulated muscle and crypt formation. In order to analyze potential effects of RA mediated by mesenchymal cells, we isolated and characterized gut mucosa mesenchyme-derived cell cultures (mesenchyme-derived intestinal cell lines, MIC). These cells were shown to express mRNAs for retinoid binding proteins similar to those expressed in situ in the intestinal mesenchyme. MIC cells co-cultured with 14-day intestinal endoderms promoted endodermal cell adhesion and growth, and the addition of exogeneous RA enhanced epithelial cell polarization and differentiation assessed by cytokeratin and lactase immunostaining. Such a differentiating effect of RA was not observed on endodermal cells when cultured without a mesenchymal feeder layer or maintained in conditioned medium from RA-treated MIC cells. In the co-cultures, immunostaining of laminin and collagen IV with polyclonal antibodies, as well as alpha1 and beta1 laminin chains mRNAs (analyzed by RT-PCR) increased concurrently with the RA-enhanced differentiation of epithelial cells. It is worth noting that this stimulation by RA was also obvious on the mesenchymal cells cultured alone. These results show that RA plays a role in intestinal morphogenesis and differentiation. In addition, they indicate that RA acts on the mesenchymal cell phenotype and suggest that RA may modify the mesenchymal-epithelial cell interactions during intestinal development.
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PMID:Mesenchyme-mediated effects of retinoic acid during rat intestinal development. 919 Oct 46


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