Biomedical subjects

G E Wild

Publications and source records attributed to G E Wild.

27 records · Page 2Linked to original sources

PubMed1996

Nutrients and intestinal adaptation.

The authors review the physiological, cellular and molecular aspects of the patterns, mechanisms and signals of the adaptation of intestinal transport of sugars and lipids, especially in response to manipulations of dietary lipid content. In models of intestinal adaptation, nutrient uptake is enhanced by an up- or down-regulation of the maximal rate of carrier-mediated transport or by alterations in the passive permeability properties (Pd) of the intestinal brush border membrane (BBM). The importance of unstirred water layers has been demonstrated. Alterations in the Pd for lipid uptake are due to changes in the lipid content of the BBM, which in turn are associated with alterations in the activity of lipid-metabolizing enzymes in the enterocyte microsomal membrane (EMM), and, therefore, alterations in the lipid composition of the EMM. Lipid uptake is also mediated by at least two proteins in the BBM, the sodium-hydrogen exchangers and the membrane-fatty-acid-binding protein. Alterations in the maximal transport rate for glucose and fructose transporters are associated with variations in the abundance of their transporters (including sodium-dependent glucose transporter, glucose and fructose transporter and fructose transporter) in the basolateral membrane sodium-potassium adenosine triphosphatase, and in the abundance of the messenger RNA of the transporters. Isocaloric changes in dietary lipids, such as switching from a saturated to a polyunsaturated diet, within the range seen in human consumption, leads to major alterations in passive and active transport processes. In a proposed model, changes in dietary lipids stimulate intracellular second messengers, modifying gene expression of the transporter carriers and of the EMM lipid-metabolizing enzymes. Thus, an understanding of the mechanisms of intestinal adaptation lays the groundwork for future studies of dietary manipulations. It may also lead to dietary interventions to prevent unwanted or to enhance desirable intestinal adaptation, thereby preventing disease.

Adaptation, Physiological↗

PubMed1995

Na(+)-K(+)-ATPase alpha 1- and beta 1-mRNA and protein levels in rat small intestine in experimental ileitis.

Na(+)-K(+)-adenosinetriphosphatase (ATPase) plays a key role in the absorption of electrolytes, water, and nutrients from the small intestine. The expression of Na(+)-K(+)-ATPase was examined in isolated enterocytes during the course of the ileal inflammatory response elicited by intraluminal administration of 2,4,6-trinitrobenzenesulfonic acid. The ileal inflammatory response was characterized by a marked cellular infiltrate, villous atrophy, and crypt hyperplasia along with fibrosis and smooth muscle hypertrophy. Peak levels of myeloperoxidase were observed at day 7, and ileal mucosal injury was paralleled by increases in ileal mucosal permeability. Ileal enterocytes were harvested from days 3 to 30 after the induction of ileitis. Decreases in Na(+)-K(+)-ATPase functional activity were observed from days 3 to 21 and were accompanied by corresponding decreases in Na(+)-K(+)-ATPase pump abundance, alpha 1- and beta 1-protein expression, and mRNA abundance, whereas Na(+)-K(+)-ATPase turnover, Michaelis-Menten constant values, and inhibition constant values for Na+ and ouabain, respectively, were unaltered. Alterations in transcriptional and posttranscriptional events may determine the changes in Na(+)-K(+)-ATPase activity in this particular model. Additionally observed increases in thymidine kinase and ornithine decarboxylase activities appear to signify alterations in the state of differentiation of the ileal epithelium and may determine the phenotypic expression of enterocyte transporters and permeability in the setting of inflammation.

Animals↗

PubMed1993

Effect of exogenously administered polyamine on the structural maturation and enzyme ontogeny of the postnatal rat intestine.

The factors regulating the developmental changes in intestinal morphology and enzyme activity during the postnatal period are incompletely understood. Increased ornithine decarboxylase (ODC) and polyamine levels occur in association with increased mucosal growth seen just prior to weaning. The present work examines the effects of the polyamine spermidine, administered exogenously during early postnatal development in the rat, on structural and functional differentiation of the intestine. Young rats were fed 6 mumol of spermidine for either 1 day (P1) or 3 days (P3) prior to sacrifice on postnatal day 10. Control littermates were sacrificed at day 10 (C10) or at day 49 (C49) (postweanling [adult] reference). A loss of most of the well-developed characteristic endosomal complex and supranuclear giant lysosome was observed in the absorptive cells of the ileum and proximal colon in the spermidine-treated groups and was accompanied by a decline in N-acetyl-glucosaminidase activity to adult levels. A precocious appearance of sucrase and NaK ATPase activities was observed in the P1 group and these activities attained adult levels in the P3 group. This premature appearance of sucrase and NaK ATPase activities was associated with a decline in lactase levels. The exogenous administration of spermidine also elicited an increase in mucosal ODC activity.

Acetylglucosaminidase↗

PubMed1992

Alterations in quantitative distribution of Na,K-ATPase activity along crypt-villus axis in animal model of malabsorption characterized by hyperproliferative crypt cytokinetics.

The distribution of sodium- and potassium-stimulated ATPase (Na,K-ATPase) along the crypt-villus axis and crypt cytokinetics were examined in an infective model of celiac disease produced by infection of the rat with the nematode Nippostrongylus brasiliensis. In controls, levels of enzyme activity remained stable during enterocyte migration to the villous apex. In the jejunum of infected rats, the structural lesion of villous atrophy and crypt hyperplasia, observed at day 10 of infection, was associated with a three-dimensional expansion of the crypts. Cell cycle time was shortened and this resulted in a markedly increased crypt cell production rate. Enterocytes emerged from the crypts at a faster rate, and this functional immaturity was paralleled by decreased Na,K-ATPase activity. Further decreases in enzyme levels were observed during enterocyte migration along the villi. This may reflect enterocyte damage or increased enzyme turnover. In the ileum of these animals, enterocyte maturation was prolonged and enzyme activity was increased at the level of the crypt villus junction with further increases noted during enterocyte transit. These changes in ileal Na,K-ATPase appear to be adaptive.

Animals↗

PubMed1989

Changes in Na,K-ATPase, sodium ion, and glucose transport in isolated enterocytes in an experimental model of malabsorption.

Nippostrongylus brasiliensis infection of the rat resulted, at day 10 of infection, in decreased levels of jejunal enterocyte sodium-potassium-activated adenosine triphosphatase (Na,K-ATPase) and potassium-activated p-nitrophenyl phosphatase (K-pNPPase) activities. Parallel decreases occurred in active sodium efflux from jejunal enterocytes in the presence and absence of actively transported monosaccharides. Ileal enterocyte Na,K-ATPase and K-pNPPase activities were significantly increased, as was active sodium efflux. In contrast to controls, the presence of monosaccharides produced a stimulation of active sodium efflux from ileal enterocytes derived from infected rats. Enzyme and sodium transport changes in the jejunal enterocytes probably reflect cellular immaturity. Functional changes in ileal enterocytes probably represent a compensatory phenomenon.

Animals↗

PubMed1980

Effect of fasting on Na-K-ATPase activity in rat small intestinal mucosa.

The effect of fasting on mucosal Na-K-ATPase activity in various regions of rat small intestine was investigated. Fasting (17--48 h) was associated with a consistent decrease in specific and total activity of Na-K-ATPase in the jejunum, the levels tending to rise more distally. No effect on the specific activities of Mg-ATPase or alkaline phosphatase was found. Fasting was also associated with incresed adrenocortical activity and with decreases in mucosal mass, protein content, and histological dimensions of the jejunum, no similar changes being found in the distal small intestine. Glucose ingestion prevented the decrease in jejunal enzyme activity associated with fasting and elevated levels in the mid and terminal small intestine of fed animals. These effects suggest that Na-K-ATPase activity in small intestinal mucosa may be, in part, inducible.

Alkaline Phosphatase↗

PubMedDate not supplied

Small bowel review--Part I.

The small bowel has undergone intense study. Part I of this two-part review of the small bowel focuses on gastrointestinal peptides; intestinal infections and human immunodeficiency virus; drugs; intestinal growth-mucosal proliferation and differentiation; nucleic acids, nucleotides and nucleosides; vitamins and minerals; Whipple's disease; radiation; and early development.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Applications of recombinant DNA technology in gastrointestinal medicine and hepatology: basic paradigms of molecular cell biology. Part C: protein synthesis and post-translational processing in eukaryotic cells.

The translation of mRNA constitutes the first step in the synthesis of a functional protein. The polypeptide chain is subsequently folded into the appropriate three-dimensional configuration and undergoes a variety of processing steps before being converted into its active form. These processing steps are intimately related to the cellular events that occur in the endoplasmic reticulum and Golgi compartments, and determine the sorting and transport of different proteins to their appropriate destinations within the cell. While the regulation of gene expression occurs primarily at the level of transcription, the expression of many genes can also be controlled at the level of translation. Most proteins can be regulated in response to extracellular signals. In addition, intracellular protein levels can be controlled by differential rates of protein degradation. Thus, the regulation of both the amounts and activities of intracellular proteins ultimately determines all aspects of cell behaviour.

Biological Transport↗

PubMedDate not supplied

Short-chain fatty acids increase proglucagon and ornithine decarboxylase messenger RNAs after intestinal resection in rats.

BACKGROUND: Intestinal adaptation is a complex physiological process that is not completely understood. Systemic administration of short-chain fatty acids (SCFAs) has been shown to facilitate adaptation to small bowel resection; however the mechanisms underlying this phenomena are unknown. METHODS: Forty-six male Sprague-Dawley rats underwent an 80% jejunoileal resection and jugular catheterization. After surgery, rats were randomly assigned to receive standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous TPN supplemented with SCFAs. On day 3 or 7 after surgery, ileal samples were removed for determination of mucosal wet weight, DNA, RNA, and protein concentrations. Total cellular RNA was extracted for use in Northern blot analysis to quantify proglucagon and ornithine decarboxylase messenger RNAs (mRNAs). RESULTS: Total, mucosal, and submucosal weights were increased (p < .05) in the SCFA group both 3 and 7 days after surgery. Ileal DNA and RNA concentrations were increased (p < .05) in the SCFA group at both time points; however ileal protein concentration did not differ between groups until 7 days after resection. Levels of proglucagon and ornithine decarboxylase messenger RNAs were higher (p < .05) in the SCFA group at both time points. CONCLUSION: The upregulation of proglucagon and ornithine decarboxylase gene expression may be the mechanism by which SCFAs facilitate intestinal adaptation.

Adaptation, Physiological↗