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Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At birth, the mammalian gastrointestinal tract (GIT) must be able to support a shift from mainly parenteral nutrition in the fetus (via the placenta) to enteral nutrition in the neonate. In the perinatal period the GIT therefore undergoes enhanced growth as well as morphological and functional differentiation, and this maturational programme is influenced by a complex interplay of local, systemic and luminal factors. This review shows how systemic and luminal factors may influence GIT development in the perinatal period of the pig and sheep, two long-gestation species. Adrenocortical hormones play a pivotal role in the prepartum maturation of the GIT in addition to their better known effects on the development of many other tissues and body systems. More particularly, in the fetal pig and sheep, the prenatal development of gastric acid and gastrin secretion, and of GIT hydrolase activities (chymosin, pepsin, amylase, lactase, aminopeptidases) is influenced by cortisol. Additionally, glucocorticoids exert effects throughout the GIT by influencing morphological, cytological, and functional differentiation. Since the GIT epithelial cells comprise a renewing cell population there are also changes in cell kinetics. In addition to systemic factors, the presence of growth factors, hormones and nutrients from swallowed amniotic fluid (fetus) and colostrum (neonate) may influence GIT development. In utero, fetal fluid ingestion has been shown to modulate tissue growth, macromolecule and immunoglobulin transport, enterocyte differentiation, cell turnover and activity of brush-border hydrolases. These effects may be mediated via regulatory peptides (e.g. insulin-like growth factor I, gastrin-releasing peptides, insulin, epidermal growth factor, gastrin). A physiological role of luminally derived growth factors is supported by a number of unique structural and functional adaptations of the GIT in the fetus and neonate (low luminal proteolysis, intestinal macromolecule transport). Thus, in the pig and sheep, both systemic and luminal factors appear to play critical roles in GIT development in the perinatal period.
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PMID:Systemic and luminal influences on the perinatal development of the gut. 935 1

The mechanism(s) by which insulin enhance prematurely the activity of brush border membrane (BBM) hydrolases in rat immature intestine is unknown. Therefore, we have compared the responses of four BBM enzymes [sucrase-isomaltase (SI), maltase, lactase-phloridzine hydrolase (LPH), and aminopeptidase] with exogenous insulin, the analog B-Asp10, IGF-I, and antireceptor MAb [insulin-receptor (IR) MAb] given to preweaning pups. Low doses of insulin caused a precocious induction of SI and of SI mRNA and stimulated maltase activity without effect on LPH nor on aminopeptidase activities. IGF-I given at the same dose as that of insulin had no detectable effect on these enzymes. Administration to sucklings of IR MAb prevented the effect of endogenous insulin by inhibiting the expression of SI and maltase without effect on LPH activity. B-Asp10, an insulin analogue that exhibits in vitro a 3.5-fold increase in receptor affinity with sustained signaling of the receptor tyrosine kinase, caused an overexpression of SI by 3.5-fold and of maltase by 1.5-fold compared with equivalent doses of normal insulin. The premature increases in SI activity, SI mRNA, and maltase activity in response to insulin were dose-dependent and were associated with dose-dependent increases in intracellular spermine and spermidine concentrations. In conclusion, these data suggest that the premature induction of SI by insulin is mediated by a dose-dependent signal initiated by binding of the hormone to its intestinal receptor, which after transduction into the cell indirectly triggers the transcription of the SI gene, possibly by changes in intracellular polyamine concentrations.
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PMID:Premature stimulation of rat sucrase-isomaltase (SI) by exogenous insulin and the analog B-Asp10 is regulated by a receptor-mediated signal triggering SI gene transcription. 958 3

Several lines of evidence suggest an important role for insulin in the regulatory mechanism of rodent small intestinal development. To investigate its potential implication in human gut, the immunofluorescent localization of insulin receptors (IR) and the influence of insulin (30 microU or 3 mU/ml) on [3H]-thymidine incorporation and on lactase and alkaline phosphatase activities were studied in fetal jejunum and colon (14-19 weeks). We demonstrate the early presence of IR, mainly detected in the basolateral portion of enterocytes and colonocytes along the crypt-villus axis. Insulin increased [3H]-thymidine incorporation as well as epithelial labeling indices in cultured explants from jejunum and colon without affecting enzymic activities. This study establishes, for the first time, that insulin stimulates proliferation of epithelial cells expressing IR in both segments without affecting brush border hydrolases in the developing human gut.
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PMID:Insulin modulates cellular proliferation in developing human jejunum and colon. 992 1

The primary factors in feeding premature infants are dependent on the development and maturation of digestion and absorption. The maturation of digestive and absorptive functions of carbohydrates, proteins, fats, minerals, and vitamins in the young premature infant were determined in relation to availability of hydrolytic enzymes, such as lipases, proteases, amylases, glucosidases, and lactase. The feeding is dependent on the ability of the premature infant to secrete salivary enzymes, gastric acid, pepsin, pancreatic exocrine enzymes, the presence of enterohepatic circulation, and the hydrolytic and absorptive capacity of the entercocyte. To evaluate the complexity of the gut maturation process, we proposed a unified concept where the ontogeny of the gastrointestinal system is the result of the following four major determinants: genetic endowment, intrinsic developmental and biological clock, endogenous regulatory mechanisms, and environmental influences. The developmental clock represents a predetermined temporal sequence of happenings in ontogeny that is inherently controlled. By 20 weeks of gestation, the anatomic differentiation of the fetal gut has progressed to the extent that it resembles that of a newborn. Secretory and absorptive functions, however, develop at different rates; the intestinal absorptive process is only partially available before 26 weeks of gestation, whereas gastric and pancreatic secretion is only basal and can be stimulated only partially even in the full-term newborn period. Regulatory mechanisms control the expression of the genetic endowment at various stages in gastrointestinal development. Neural-hormonal factors play major roles in the ontogeny of the gut. Adrenalectomy, hypophysectomy, and thyroidectomy delay the development of the gut. Administration of glucocorticoids or thyroxine at the critical stage in maturation causes early appearance of enzymes within the intestine. Other hormones that are potentially important in regulating gastrointestinal development include cholecystokinin, gastrin, secretin, which have trophic effects on the gastrointestinal tract, and insulin, insulin-like growth factors, and epidermial growth factor. The development of gastrointestinal secretory function, particularly in response to hormonal stimulation, has received considerable attention. The degree of response of the target cell is determined not only by the amount of effective hormone reaching it but also by the number and affinity of receptors on its surface. Human newborns have high levels of gastrin in their sera, yet have low acid output. Exogenous gastrin is an ineffective stimulant despite the presence of seemingly "anatomically developed" parietal cells. It seems that neither endogenous nor exogenous gastrin has an effect on the target cell. If one accepts the role of circulating gastrin levels in the regulation of its own receptor, one can hypothesize the absence of a regulatory effect of gastrin in the newborn period. It was shown that hormonal regulation of migrating activity by motilin is also absent in the preterm and term infant. Plasma levels of motilin in neonates are comparable to those found in adults, but migrating motor complexes occur in the absence of cycling of plasma concentrations. Interestingly, however, the motilin receptor appears to be present. In conclusion, the feeding mode content, concentration, and volume of the very young premature infant can be assessed by the development of digestive and absorptive capacity and gut motility. The concomitant changes in gut hormones and regulatory peptides during ontogeny and feeding will add a new dimension in the understanding of when, what, and how to feed the very young premature infant.
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PMID:The ontogeny of the small intestinal epithelium. 1048 84

Although mitogen-activating protein (MAP) kinases are crucial signal transduction molecules regulating cellular proliferation, differentiation, and morphology, their ontogenic changes in the small intestine have not been analyzed. Also, it remains unknown which pathway of activated MAP kinases regulates the expression of brush border membrane hydrolases during growth. Therefore, we have analyzed the mucosal distribution, ontogeny, and responses to insulin and to inhibitors of p44, p42, and p38 MAP kinases in immature and mature enterocytes using Western blot analysis and autoradiography after immunoprecipitation, immunohistochemistry, and in vitro phosphorylation assays. Between d 10 and 40 postpartum, diphosphorylated active p44/p42 extracellular regulated protein kinases (ERKs) increased in abundance compared with total immunoprecipitated ERKs, and were highly responsive to exogenous insulin. In concordance, ERK total activity increased by 4-fold during the same period of growth and was further enhanced 2-fold by exogenous insulin. In weaning rats, ERKs were mainly located in membranes of villus cells and with less intensity in crypt cells. By contrast, p38 MAP kinase was unresponsive to insulin and was confined to nuclei. Administration to sucklings of PD 098059, a specific inhibitor of ERKs, not only inhibited the premature stimulation of sucrase, lactase, and maltase total activities in response to exogenous insulin, but also depressed the natural expression of these brush border membrane enzymes in the absence of insulin stimulation. In concordance, administration of SB 203580, a specific inhibitor of p38 MAP kinase, failed to inhibit both the response of brush border membrane hydrolases to insulin and their natural expression in the absence of insulin stimulation. We conclude that the ontogenic expression of brush border membrane hydrolases and their premature stimulation by insulin are regulated at least in part by the activation of p44/p42 ERKs but not by p38 MAP kinase.
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PMID:Ontogeny of MAP kinases in rat small intestine: premature stimulation by insulin of BBM hydrolases is regulated by ERKs but not by p-38 MAP kinase. 1214 94

Milk-borne insulin-like growth factors (IGFs) enhance nutrient absorption in the immature intestine, which is characterized by low levels of glucose oxidation. We therefore hypothesized that feeding a rat milk substitute (RMS) devoid of growth factors to rat pups would lower serum glucose levels relative to dam-fed control rats and that supplementation of RMS with physiological doses of either IGF-I or IGF-II would normalize serum glucose levels via increased jejunal glucose transporter 2 (GLUT2) and high-affinity Na(+)-glucose cotransporter (SGLT1) expression. We found lower serum glucose concentrations in RMS-fed pups; in contrast, serum glucose levels in the IGF-supplemented pups were similar to those of dam-fed controls. RT-PCR and laser scanning confocal microscopy similarly demonstrated that IGF supplementation increased expression of jejunal glucose transporters. Further experiments demonstrated that IGF supplementation altered mRNA levels of key mitochondrial enzymes without altering jejunal lactase activity. We conclude that IGF-I and IGF-II supplementation increases serum glucose levels in the immature rat pup fed artificial formula and alters gene expression of the jejunal glucose transporters.
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PMID:IGF alters jejunal glucose transporter expression and serum glucose levels in immature rats. 1238 63

Insulin-like growth factors-1 and -2, IGFBP-2 and -3, and receptors for IGF type-1 and type-2 (IGF-1R, IGF-2R), growth hormone (GHR), and insulin (InsR) in neonatal calves are variably expressed among gastrointestinal sites and thought to exert site-specific physiological functions. We studied by real-time reverse-transcription PCR, whether there are differences in the abundance of mRNA coding for IGF-I, IGF-2, IGFBP-2, IGFBP-3, IGF-1R, IGF-2R, GHR, and InsR in compartmentalized layers (fractions) of jejunum and ileum of 5-d-old calves fed colostrum. Samples of jejunum consisted primarily of villi and crypts; samples from ileum consisted mainly of villus tips, crypts, and lamina propria (LP; containing mainly Peyer's patches). After slaughter, segments of middle areas of jejunum and ileum were flushed with 154 mM NaCl. Pieces (5 mm x 5 mm) of jejunal (n = 9) and ileal walls (n = 5) were placed on glass slides and snap-frozen in liquid N before being cut horizontally into 10-mum-deep slices using a cryotome at -20 degrees C. Fifteen consecutive and morphologically similar slices were collected as fractions of villus, crypt, and LP layers, respectively. Fractions were characterized by use of 5'-bromo-2-deoxyuridine (BrdU) that labeled proliferating cells, and by expression of lactase mRNA. The BrdU-labeled cells were present in crypts and LP, but not in tips of villi. Lactase mRNA levels were greater in villus than crypt fractions, but lactase mRNA was absent in LP. In jejunum, mRNA levels, relative to levels of housekeeping genes (sum of levels of mRNA coding for ubiquitin, glyceraldehyde phosphate dehydrogenase, beta-actin, and ribosomal RNA), differed (P < 0.05) between fractions for InsR (crypts > villi), IGFBP-2 (crypts > villi), and IGFBP-3 (crypts > villi), and total RNA levels were greater (P < 0.05) in crypt than villus fractions. In ileum, mRNA levels, expressed relative to housekeeping genes, differed (P < 0.05) between fractions for IGF-I (LP > villi, crypts), IGF-2, and IGFBP-3 (villi > crypts, LP), GHR and InsR (crypts > LP), IGFBP-2 (crypts > villi, LP), and total RNA levels were greater (P < 0.05) in LP and crypt than in villus fractions. In conclusion, the tested fractionation technique is quite applicable for gene expression studies in the intestine of calves. Members of the somatotropic axis and of the insulin receptor are not equally expressed in different jejunal and ileal layers of neonatal calves.
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PMID:Abundance of mRNA encoding for components of the somatotropic axis and insulin receptor in different layers of the jejunum and ileum of neonatal calves. 1554 64

This study aims to estimate the tolerable lactose intake which can be utilized in the digestion by lactase and in the fermentation by intestinal microbes in Japanese female adults. The first, the maximum permissive dosage of lactose not to induce transitory diarrhea was estimated based on the oral ingestion of lactose at several dose levels in all the subjects, and compared with that of lactitol which is not hydrolyzed by digestive enzymes. A second lactose tolerance test involving 10 g and 30 g of lactose was carried out in 10 subjects showing resistance to diarrhea, and serum glucose and insulin levels and the amount of hydrogen excreted in the breath were measured for comparison with those of glucose and lactitol. Subjects were 43 Japanese female adults (average: age 20.5+/-2.1 y, weight 51.3+/-5.1 kg) who had not been diagnosed as having either hypolactasia or being lactose intolerant. Serum glucose and insulin levels were scarcely elevated following the ingestion of both 10 g and 30 g of lactose, while the amount of hydrogen excreted in the breath was greatly increased following the ingestion of 30 g of lactose, but these levels were less following the ingestion of 10 g of lactose. In contrast, the ingestion of 15 g of glucose significantly increased blood glucose and insulin levels, while no hydrogen was detected in the breath. The maximum permissive dosage of lactose not to induce transitory diarrhea was 0.72 g/kg of body weight and that of lactitol was 0.36 g/kg of body weight in Japanese adults. The digestive capacity of lactase is less than 10 g of lactose by single ingestion, while intestinal microflora are able to ferment approximately 20-30 g of lactose. In addition, the ingestion of more than 10 g of lactose might be contributed as prebiotics.
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PMID:Maximum permissive dosage of lactose and lactitol for transitory diarrhea, and utilizable capacity for lactose in Japanese female adults. 1602 89

The postnatal development of intestine is associated with a decline in brush border lactase activity in rodents. This is similar to adulthood hypolactasia, a phenomenon prevalent in humans worldwide. In the present study, the effect of luminal proteases from adult rat intestine was studied in vitro on intestinal lactase activity in saline control, thyroxine, insulin and cortisone treated rat pups. Lactase levels were determined by enzyme analysis and Western blotting. mRNA levels encoding lactase were determined by Northern blotting. Administration of thyroxine for 4 days reduced (P<0.05) lactase activity, but insulin treatment had no effect in 8-day-old rat intestine. However, cortisone administration augmented (P<0.01) lactase activity, under these conditions. Western blot analysis showed decreased lactase signal corresponding to 220-kDa protein band in thyroxine treated animals. However, the intensity of lactase signal was high in cortisone treated animals compared to controls. mRNA levels encoding lactase showed a 6.8-kb mRNA transcript in saline and hormone treated rats. mRNA levels encoding lactase were increased in cortisone treated animals but were reduced in thyroxine injected pups compared to controls. Microvillus membranes from saline (P<0.01) and thyroxine (P<0.05) or insulin (P<0.01) treated rats upon incubation with luminal wash from adult rat intestine showed a significant decline in lactase activity. These findings suggest that thyroxine, insulin or cortisone induced changes in lactase expression in suckling rat intestine make it susceptible to luminal proteases, which may in part be responsible for observed maturational decline in lactase activity in adult rat intestine.
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PMID:Hormone induced expression of brush border lactase in suckling rat intestine. 1827 61

Lactase exists in both soluble and membrane-bound forms in suckling rat intestine. The distribution of lactase and its glycosylated isoforms in response to thyroxine or cortisone administration has been studied in suckling rats. 75% of lactase activity was detected, associated with brush borders, compared to 24% in the soluble fraction of 8-day-old rats. Thyroxine treatment enhanced soluble lactase activity to 34%, whereas particulate fraction was reduced to 67% compared to controls. Cortisone administration reduced soluble lactase activity from 24% in controls to 12% with a concomitant increase in membrane-bound activity to 89%. Western blot analysis revealed lactase signal, corresponding to 220 kDa in both the soluble and membrane fractions, which corroborated the enzyme activity data. The elution pattern of papain solubilized lactase from agarose-Wheat Germ agglutinin, or Concanavalin A or Jacalin agglutinin columns was different in the suckling and adult rat intestines. Also the elution profile of lactase activity from agarose-lectin columns was modulated in cortisone, thyroxine, and insulin injected pups, which suggests differences in glycosylated isoforms of lactase under these conditions. These findings suggest the role of these hormones in inducing changes in lactase glycosylation during postnatal development of intestine, which may contribute to adult-type hypolactasia in rats.
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PMID:Hormone induced changes in lactase glycosylation in developing rat intestine. 1871 86


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