Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.26 (invertase)
4,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MDL 25,637 is a novel compound designed as a transition-state inhibitor of alpha-glucohydrolases. This compound inhibits rat intestinal sucrase, maltase, isomaltase, glucoamylase and trehalase activities at micromolar concentrations. It is a much weaker inhibitor of alpha-amylase and lactase. Inhibition of sucrase was competitive with sucrose. In mice, MDL 25,637 inhibited the rise in serum glucose after a sucrose or starch load but not after a glucose load. MDL 25,637 also reduced the glycemic response to sucrose in rats. The drug was most effective when administered 0 to 30 min before the sucrose load and was as effective in streptozotocin-treated rats as in normals. The inhibition by MDL 25,637 of intestinal glucohydrolases is an effective means of reducing the hyperglycemic response to an oral sucrose or starch load and, as such, warrants further investigation as a potential drug for the treatment of diabetes mellitus.
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PMID:Inhibition of intestinal disaccharidases and suppression of blood glucose by a new alpha-glucohydrolase inhibitor--MDL 25,637. 329 22

1. Injection of hydrocortisone into 9-day-old rats induces the early appearance of sucrase in jejunal homogenates, the time course of the subsequent increase and magnitude of the final effect being similar to that seen to start on day 16 during normal development. 2. Cytochemical comparison of the effect of hydrocortisone and normal development on the appearance of a mixture of sucrase, maltase, isomaltase and trehalase disaccharidases (alpha-glucosidase activity) shows this enzyme to appear first in enterocytes at the base of the villus. Enzyme activity then increases and spreads along the whole villus during the next 96 h. 3. The rate at which enterocytes migrate along the villus after hydrocortisone injection is not significantly different from that measured during the early phase of normal development. The later phase of normal development is associated with a threefold increase in cell migration rate and a twofold increase in crypt depth. 4. The rate at which alpha-glucosidase activity increases in enterocytes at the base of the villus during early normal development is similar to that determined after hydrocortisone injection into younger animals. This rate of appearance increases eight to tenfold during normal development, shortly after the appearance of solid food in the stomach of normal control animals. 5. Injection of steroid hormones into young rats is generally supposed to mimic events taking place normally at weaning. Present results show alpha-glucosidase induction during normal development to be under more complicated control than had been previously suspected.
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PMID:Rat jejunal disaccharidase activity increases biphasically during early post-natal development. 332 44

The direct influence of epidermal growth factor (EGF) on the differentiation and proliferation of small intestine was studied in organ culture. Eight-day-old mouse small intestine was cultured during 2 days in serum-free Leibovitz L-15 medium alone or supplemented with EGF (50, 100, and 500 ng/ml) either at room temperature or at 37 degrees C. Brush border membrane hydrolytic activities, namely, sucrase, lactase, glucoamylase, trehalase, maltase, and alkaline phosphatase, were assayed in the intestinal tissue as well as in the culture medium. None of the brush border enzymic activities was affected by the addition of EGF to the culture medium. This lack of effect is not temperature dependent since it occurred both at room temperature and at 37 degrees C. The addition of hydrocortisone (10(-6) M) to the culture medium induced the appearance of sucrase activity and increased the activity of the other brush border enzymes. The simultaneous addition of EGF with hydrocortisone did not influence the response of the intestinal explants to hydrocortisone. The deoxyribonucleic acid (DNA) content was determined while DNA synthesis was evaluated by the incorporation of (3H)-thymidine. The addition of EGF did not affect DNA content or (3H)-thymidine incorporation into DNA either at room temperature or at 37 degrees C. The EGF binding to epithelial cells did not significantly vary throughout the culture period and a down-regulation process occurred in presence of EGF. These observations strongly suggest that EGF does not act as a primary cue for inducing developmental changes in suckling mouse small intestine. It is proposed that EGF induces a systemic reaction in vivo that then influences the neonatal small intestine.
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PMID:Epidermal growth factor does not act as a primary cue for inducing developmental changes in suckling mouse jejunum. 349 91

Human fetal colon (14-16 weeks gestation) was cultured as explants for 15 days in serum-free Leibovitz L-15 medium at 37 degrees C. The overall morphology of the colonic explants was well maintained throughout the culture period and all epithelial cell types retained their ultrastructural characteristics. The incorporation of [3H]-leucine continued and even increased, reflecting sustained synthesis of proteins. Even though the incorporation of [3H]-thymidine into the total DNA decreased during culture, the synthesis of DNA continued. The sites of [3H]-thymidine incorporation into the different layers of the colonic wall were studied by radioautography. The incorporation of the radioactive precursor occurs mainly in the epithelium and to lesser degrees in the mesenchyme and the muscular layer. Labeled epithelial nuclei were located in the intervillous areas but not on the villi. The labeling index of the epithelial cells remained constant throughout the culture period indicating the preservation of the proliferative capacity of the epithelium. Brush-border hydrolytic activities, namely those of sucrase, maltase, lactase, trehalase, glucoamylase and alkaline phosphatase, were assayed in the colonic tissue. These enzymic activities generally decreased in the tissue and increased in the medium during the course of culture. These observations clearly demonstrate that fetal colon can be maintained viable for at least 15 days in a serum-free medium. Organ culture now provides the opportunity to study the normal function and metabolism of human colon during its development.
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PMID:Human fetal colon in organ culture. 368 52

Assays for sucrase carried out on intestinal sonicates prepared from 18 different strains of mice revealed a threefold variation in specific activity, the values for CBA/Ca mice being significantly less than for any other strain. Further comparison of the CBA/Ca versus the C57BL/6J mouse showed this deficiency, which became established 2-4 weeks after birth, to apply to isomaltase as well as sucrase but not to maltase or trehalase. Backcross experiments indicated that this deficiency in sucrase activity was inherited as a single codominantly expressed genetic factor. The ability of the CBA/Ca mouse to regulate sucrase activity in response to changes in diet was also reduced compared to that of the C57BL/6J mouse. No difference could be detected in the affinity of sucrase for its substrate or in the ability of heat to denature sucrase prepared from CBA/Ca and C57BL/6J mice. It is suggested that part of the regulatory region of the gene coding for sucrase-isomaltase is modified in the CBA/Ca mouse and that this locus should be given the notation Suc-1 for future reference.
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PMID:Evidence for a possible regulatory gene (Suc-1) controlling sucrase expression in mouse intestine. 372 24

The effect of 1,25-dihydroxyvitamin D3 (1,25-D) on the activity of intestinal disaccharidases, maltase, sucrase, trehalase and lactase, was studied in five-sixths nephrectomized uremic rats. In uremic rats, maltase, sucrase and trehalase activities were lower than in sham-operated rats. Administration of 1,25-D produced significant improvement of maltase, sucrase, trehalase and lactase activities in uremic rats. These results suggest that activities of intestinal disaccharidases are reduced in uremic rats and these activities are normalized after 1,25-D administration.
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PMID:Effect of 1,25-dihydroxyvitamin D3 on intestinal disaccharidases in uremic rats. 375 7

The purpose of this work was to study the direct influence of epidermal growth factor (EGF) on the maturation of the fetal mouse duodenum in organ culture. Duodenal explants, resected at 17 days of gestation, were cultured during 48 h at 37 degrees C in Leibovitz L-15 serum-free medium alone or supplemented with EGF (100 ng/ml). Differentiation of absorptive cells was evaluated by measuring brush border hydrolytic activities. After 48 h of culture with and without EGF, villous architecture and the fine structural characteristics of the tissues are preserved. In control explants, the level of alkaline phosphatase, maltase, trehalase, and sucrase activities as well as the protein and DNA contents remain comparable to the values measured in 17-day explants at the beginning of the culture period, while lactase activity falls drastically. In explants cultured with EGF, the level of alkaline phosphatase, maltase, and trehalase activities and the protein contents significantly increase while sucrase activity and DNA contents are unchanged, and lactase activity remains under the onset level. From these results, it was concluded that EGF influences directly the maturation of some brush border enzymes in the duodenum during the fetal period.
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PMID:Influence of epidermal growth factor on the maturation of the fetal mouse duodenum in organ culture. 387 51

High doses of 16,16-dimethyl prostaglandin E2 (dmPGE) are trophic to the small bowel of adult and suckling rats. In suckling rats this effect is paralleled by an increase in brush border enzyme activities, possibly indicating accelerated mucosal maturation. To investigate the possible physiological significance of this phenomenon, we examined whether this induction of intestinal enzyme activities can be reproduced in adult rats and whether cell growth and enzyme activity might be suppressed by indomethacin. Treatment twice daily for 2 weeks with 100 micrograms/kg dmPGE by intragastric instillation increased villus length in the proximal and distal small bowel by 36% and 40%, respectively, while 2 mg/kg indomethacin by subcutaneous injection had no effect. Maltase, trehalase, lactase, and sucrase activities were unchanged after dmPGE or indomethacin. [3H]-thymidine incorporation into DNA was not significantly influenced for up to 24 h after a single dose of both 100 micrograms/kg PGE intragastrically or 10 mg/kg indomethacin subcutaneously. These studies confirm that in adult rats large doses of 16,16-dm PGE2 increase the volume of the small-bowel mucosa. In contrast to the situation in suckling rats, the activity of hydrolytic brush border enzymes is not increased. There is thus no evidence that endogenous prostaglandins are trophic or influence brush border enzymes in the adult rat.
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PMID:Influence of 16,16-dimethyl prostaglandin E2 on morphology and brush border enzymes of small-bowel mucosa. Differences in reactivity between adult and suckling rats. 392 42

In adult sparse-fur mutant mice, ornithine transcarbamylase (OTC) activity represents only 14% of the normal values. We studied the development of this activity from birth to adult period and demonstrated that the enzyme deficiency is already fully expressed at birth, in both the liver and the small intestine of mutants. Since OTC catalyzes the conversion of ornithine to citrulline, in the presence of carbamoyl-phosphate, the effect of a disturbed ornithine metabolism on the postnatal development of the small intestine has been evaluated. The normal appearance of sucrase as well as the normal increase of glucoamylase, trehalase, and alkaline phosphatase activities are delayed in sparse-fur mice compared with controls. Moreover, normal adult values are never attained. In contrast, the normal decline of lactase activity is impaired while leucylnaphthylamidase activity is unaffected. Cell proliferation, as evaluated by [3H]thymidine incorporation into DNA and mitotic index, is less active during the 3rd wk of life in mutants. These phenomena are closely associated with a transient weak arginase and ornithine decarboxylase activity in the small intestine. Since arginase catalyzes the conversion of arginine to orthithine, thus ensuring the availability of this substrate for ornithine decarboxylase activity, these results indicate a disturbance of polyamine metabolism in mutant enterocytes with a consequent delay in postnatal differentiation and proliferation. Sparse-fur mutant mouse may therefore represent a useful animal model for evaluating the role of ornithine metabolism in the maturation process of the small intestine.
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PMID:Postnatal maturation of enterocytes in sparse-fur mutant mice. 395 97

The activities of brush border membrane-associated hydrolases such as alkaline phosphatase (Alkpase), aminopeptidase, dipeptidyl aminopeptidase IV (DAP-IV), sucrase, lactase, and trehalase were studied in 14 different human colorectal cancer cell lines. The effect of sodium butyrate, a known differentiating agent, and cell growth on the activities of these enzymes was also examined. All 14 cell lines exhibited brush border membrane enzyme activities, and in general, the activity of Alkpase, aminopeptidase, and DAP-IV was much higher than the disaccharidases. However, the specific enzyme activities varied among different cell lines. The induction of Alkpase activity by sodium butyrate occurred in most of the 14 cell lines (2- to 123-fold), while induction of the other enzyme activities was observed in several (1.5- to 3.5-fold). In some instances, butyrate caused a decrease in enzyme activity. There was no statistically significant correlation between the induction of Alkpase activity and that of other enzyme activities by sodium butyrate. Levels of aminopeptidase and DAP-IV activity were found to be dependent on cell density and increased 3- to 4-fold by the tenth day in most of the cell lines. Sodium butyrate altered the subcellular distribution pattern of the disaccharidases, causing a significant increase in activity associated with the soluble (cytoplasmic) fraction. Other enzymes such as Alkpase and DAP-IV continued to be predominantly associated with the membrane fraction in butyrate-treated cells. These data suggest that brush border membrane hydrolase activity and the effect of sodium butyrate may provide useful information regarding the differentiation of human colorectal cancer cells.
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PMID:Effect of growth and sodium butyrate on brush border membrane-associated hydrolases in human colorectal cancer cell lines. 400 36


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