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)

Caco-2 cells, which express spontaneous enterocytic differentiation at confluency, is one of the most relevant in vitro models for the study of differentiation and regulation of intestinal functions. However, these cells are normally cultured in the presence of 15-20% serum which renders extremely complex the identification of the factors involved in the regulation of both proliferation and differentiation. This study has been devoted to the establishment of chemically defined culture conditions which can sustain growth and differentiation of Caco-2 cells. The replacement of serum by ITS (insulin, transferrin, and selenium) allowed for normal structural and functional differentiation of cells as revealed by the establishment of cell polarity and the expression of brush-border membrane enzyme markers (sucrase, maltase, lactase, alkaline phosphatase, gamma-glutamyltransferase, aminopeptidase N, and dipeptidyl-dipeptidase IV), although the levels of sucrase activity were lower in ITS-supplemented medium. Coating petridishes with either type IV collagen or basement membrane proteins (Matrigel) did not improve the differentiation of cells, brush-border membrane enzyme activities being, in fact, lower when the cells were grown on these substrata. When triiodothyronine (T3, 5 x 10(-8) M) was added to the ITS-supplemented medium, disaccharidase and alkaline phosphatase activities were significantly increased while gamma-glutamyltransferase activity was diminished by T3 and stimulated by epidermal growth factor (1.6 x 10(-6) M). On the other hand, hydrocortisone (HC, 10(-6) M) did not modify disaccharidase and peptidase activities. These data clearly show that Caco-2 cells can be maintained in serum-free medium and that this system allows the study of the factors involved in the regulation of the differentiation of enterocyte in vitro.
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PMID:Caco-2 cells cultured in serum-free medium as a model for the study of enterocytic differentiation in vitro. 193 45

BioBreed (BB) Wistar rats develop diabetes mellitus, which closely resembles the human disease, in 50% of progeny. Intestinal sucrase-alpha-dextrinase, a glycoprotein hydrolase of the enterocyte's brush border consisting of 140-kDa alpha-dextrinase and 125-kDa sucrase subunits, is essential for surface digestion of carbohydrate nutrients. Although its catalytic characteristics were found to be maintained in the diabetic state, the structure of the subunits, as compared with normal Wistar rats, was altered in the BB rat within 2 days of the onset of diabetes. Its capacity to react in a solid-phase immunoassay was reduced by 50%; when examined by 6% acrylamide electrophoresis, the sucrase subunit was increased in mass by 5 kDa and, in some BB rats, the dextrinase subunit was reduced by 5 kDa. Intact rats labeled intraintestinally with [35S]methionine displayed the alteration within 6 h of synthesis, indicating that nonenzymatic glycosylation could not account for the structural change. This mass change was not seen in streptozotocin-induced diabetes and was independent of the plasma glucose concentration or the degree of acidosis. Deglycosylation with peptide N-glycosidase indicated that the N-linked chains of the normal dextrinase subunit (11 kDa) have twice the mass of those in the BB rat (6 kDa) and that the sucrase subunit may have an increased mass of O-linked chains. Overall, these experiments point to changes in glycosylation as a mechanism of structural alteration in congenital diabetes. Despite persistence of the insulin-dependent diabetes, the subunit pattern eventually became indistinguishable from normal, but at differential rates (21 days and 35 days, respectively, for sucrase and dextrinase subunits).
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PMID:Sucrase-alpha-dextrinase in diabetic BioBreed rats: reversible alteration of subunit structure. 199 46

Inhibition of intestinal alpha-glucohydrolase activity is one approach for reducing the glycemic response from dietary carbohydrate and may prove useful for the treatment of diabetes mellitus. In this article, we describe the pharmacological properties of a time-dependent intestinal alpha-glucohydrolase inhibitor, MDL 73945. When preincubated 2 h with a rat intestinal mucosa preparation before substrate addition, MDL 73945 was a potent inhibitor of sucrase, maltase, glucoamylase, and isomaltase activities (MDL 73945 concentrations required to cause a 50% decrease in enzyme activity, 2 x 10(-7), 1 x 10(-6), 5 x 10(-6), and 8 x 10(-6) M, respectively); without preincubation, it was 10- to 500-fold less potent. In rats, a single oral dose of MDL 73945 administered simultaneously with 2 g/kg body wt sucrose resulted in a dose-dependent reduction in the area under the 0- to 3-h glycemic response curve, which was significant at 1 (45% reduction) and 3 (65% reduction) mg/kg. When administered 1 h before sucrose, the compound was more potent, with 0.3 mg/kg MDL 73945 significantly reducing the glycemic response to sucrose by 62%. A reduction in the glycemic response to sucrose was accompanied by reduced insulin secretion. MDL 73945 was slightly less effective against a starch load, with 3 and 10 mg/kg MDL 73945 administered 0.5 h before starch reducing the glycemic response by 39 and 52%, respectively. MDL 73945 was more effective against a sucrose load in streptozocin-administered rats than in control rats and was as effective after 16 daily doses as after a single dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New potent alpha-glucohydrolase inhibitor MDL 73945 with long duration of action in rats. 206 Jul 19

Suckling rat intestine contains 35 and 65% of the cytosolic and membrane-bound alkaline phosphatase (AP) activities. The corresponding values for sucrase were 20 and 80% respectively. The amount of the soluble enzymes was reduced to 7-11% in adult rat intestine. Administration of cortisone, thyroxine or insulin to suckling animals induced adult type distribution of the enzymes. There were apparent differences in kinetic characteristics of soluble and brush border enzymes, but the kinetic properties of the normally developed and hormone-induced AP and sucrase were essentially similar. This suggested identical nature of these enzymes under these conditions. A biphasic Arrhenius plot was obtained for AP in weaned and hormone injected pups with a break point around 18 degrees C, while the soluble enzyme yielded a monophasic curve (Ea = 8-11 kcal/mole). Arrhenius plot for sucrase was monophasic in the suckling, hormone-injected and adult rat intestine (Ea = 8.3-15.1 kcal/mole). Membrane-bound enzymes were generally labile, while soluble enzyme activities were stable to heat treatment (sucrase at 50 degrees C and AP at 60 degrees C) in various experimental groups.
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PMID:Kinetic characteristics of soluble and brush border alkaline phosphatase and sucrase activities in developing rat intestine: effect of hormones. 235 52

Allantoic endoderm of 3-day chick embryos was combined with pancreatic mesenchyme of 5-day embryos and cultured as chorio-allantoic grafts for a total of 14 days. Recombinations of endoderm and mesenchyme of the pancreas and of the allantois served as controls. The usual types of endocrine cells differentiated in the pancreatic controls, none in the allantoic controls. In experimental grafts simple columnar epithelium with goblet cells and a sucrase-positive brush border developed; a few insulin cells and endocrine cells typical of the intestine differentiated. Hence allantoic endoderm has endocrine potentiality not realised in vivo, where its own mesenchyme may be inhibitory.
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PMID:Differentiation of endocrine cells in chick allantoic epithelium combined with pancreatic mesenchyme. 247 27

This investigation was undertaken to study the effects of hormones, sugars and amniotic fluid on the maturation of brush border enzymes in the human fetal intestine, at early stages of gestation. Intestinal explants from 8-13-weeks fetuses were maintained in organ culture for 3 days in the presence of the agents to be tested. The data show that the explanation of human fetal gut in a serum free culture medium elicits a significant maturation (2-4-fold increase above preculture levels) of lactase and aminopeptidase whatever the gestational stage studied and of sucrase and alkaline phosphatase at specific stages of development. To be expressed, the overall maturation needs the presence of sugar (in particular glucose) in the culture medium. The addition of dexamethasone, insulin or amniotic fluid to the medium did not further enhance brush border enzyme activities except for lactase whose levels were doubled by the dexamethasone. The present data suggest that in addition to the differences which exist among mammalian species in the timing of enzyme development, there may be a species specificity in the factors involved in fetal enzymatic maturation.
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PMID:Maturation of brush border hydrolases in human fetal intestine maintained in organ culture. 308 14

The effect of oral administration of total soya saponins (TS) on the development of obesity induced by (GTG) injection was examined. In the GTG-obese group, the serum immunoreactive insulin (IRI) levels were significantly increased and food consumption was suggestively increased. In addition, sucrase activity in the intestinal mucosa was increased and the surface area of intestinal villi was significantly greater, suggesting enhanced gastrointestinal function. Oral administration of TS prevented development of obesity and prevented an increased level of IRI in GTG-obese animals. It also restored the sucrase activity and the surface area of intestinal villi to normal. Thus, TS may be effective in preventing development of obesity.
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PMID:Effect of soya saponins on gold thioglucose (GTG)-induced obesity in mice. 309 55

The effect of streptozotocin (SZ) on the development of small intestinal enzymes in postnatal rat pups was studied. SZ was injected ip on Day 10 and, if necessary, again on Day 12. On Days 15, 18, and 21, one pup from each group (including a vehicle-injected control (C) group) was decapitated under conditions which minimized stress. Plasma glucose, insulin (IRI), and corticosterone were measured, as were pancreatic IRI, liver glycogen, and liver membrane binding of IRI. Small intestinal segments were processed and analyzed for sucrase, lactase, maltase, and ileal acid beta-galactosidase activities. Our results indicate that plasma glucocorticoid levels remained virtually constant in both SZ and C groups, while the ontogenic profiles of sucrase and maltase in SZ rats were shifted toward an earlier appearance and a precocious maturation. Circulating levels of IRI were not reduced significantly by SZ despite the fact that pancreatic IRI was decreased 95%. Jejunal lactase, unlike data reported for diabetic rats, was not affected by SZ diabetes. Also, acid beta-galactosidase was unaltered in the SZ rat pups. It is concluded that possibly the elevated disaccharidases seen in diabetic postnatal rat pups are the direct effect of elevated blood glucose. If so, the SZ rat pup model may be a useful tool with which to study effects of glucose on intestinal enzymes in the absence of changes in plasma insulin.
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PMID:Effects of diabetes on development of small intestinal enzymes of infant rats. 312 20

Insulin has been proposed as an important factor in the regulation of growth and differentiation of the small intestine. In the newborn miniature pig, we induced significant physiologic increases in serum insulin and the insulin/glucagon ratio without altering serum glucose, beta-hydroxybutyrate, glucagon, cortisol, T3, and T4 using glucose-based total parenteral nutrition (TPN) in one group (group G) compared with a combination of glucose and fat in another group (group G/F). Control animals were sham-operated and fed a pelleted diet (group OC). Duodenal villus surface area and mucosal height were significantly greater in group G/F compared with group G. No other differences between the TPN groups were found in small intestinal growth, mucosal protein, deoxyribonucleic acid and ribonucleic acid content, and disaccharidase activities. As anticipated, group OC demonstrated increased intestinal length, weight, and villous surface area compared with the TPN groups. Ileal sucrase and jejunal and ileal maltase activities were greater in the TPN groups compared with those in group OC. Physiologic changes in serum insulin and the insulin/glucagon ratio induced by the TPN fuel mix do not appear to have altered small intestinal growth, composition, and differentiation in the healthy small intestine.
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PMID:Effect of different total parenteral nutrition fuel mixes on small intestinal growth and differentiation in the infant miniature pig. 249 81

The influence of insulin on the postnatal development of intestinal functions linked to villus cells (sucrase, lactase, maltase and aminopeptidase) and crypt cells (secretory component of immunoglobulins, SC) has been studied in suckling and weanling rats. At 9 days of age, the animals received a daily injection of insulin 12.5 mU g-1 body weight day-1 for 4 days. Compared with saline-treated controls, insulin had no effect on the development of the intestinal mucosal mass parameters determined in the jejunum, ileum and colon. A premature appearance of sucrase was noted in isolated jejunal villus and crypt cells, the level of activity reached by the enzyme being dependent of the amount of insulin injected. By 6 and 12 h after a single injection of the hormone (12.5 mU g-1 body weight), sucrase activity was detected in all the cell fractions along the villus-crypt axis. In villus cells of insulin-treated rats, maltase, lactase and aminopeptidase activities were significantly (P less than 0.001) increased (+201%, +50%, +207%, respectively, vs. controls), whereas the concentration of SC measured by a sensitive immunoradiometric assay was enhanced over the controls by 75% in villus cells, 83% in crypt cells and 172% in the liver. Weanling rats treated from day 10 to day 20 postpartum with 12.5 mU insulin also exhibited a higher intestinal production of SC (+93%, P less than 0.01) than did saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal development in the suckling rat: effect of insulin on the maturation of villus and crypt cell functions. 313 25


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