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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rat kidney- and intestine-specific cDNA (D2) that induces high-affinity, Na(+)-independent uptake of cystine and dibasic and neutral amino acids into cRNA-injected Xenopus oocytes was recently isolated by expression cloning in our laboratory (R. G. Wells and M. A. Hediger. Proc. Natl. Acad. Sci. USA 89: 5596-5600, 1992). At present it is not known whether the D2-encoded protein functions as a transporter or as a transporter activator. To gain more insight into the role of D2 in renal amino acid transport, we studied the site of its expression in the kidney. This was determined by Northern blot analysis and by using a combination of in situ hybridization and immunocytochemistry with antibodies that recognize specific proximal tubule segments. D2 antisense RNA hybridized to the same tubular segments that were strongly positive for anti-ecto-adenosinetriphosphatase but negative for carbonic anhydrase type IV and the facilitated glucose transporter GLUT2. We conclude that D2 mRNA is strongly expressed in the rat kidney proximal tubule S3 segment, although there is weak hybridization to the S1 and S2 segments. The signal is absent in all other parts of the kidney. The S3 specific expression of D2 mRNA coincides with the site of high-affinity transport of cystine and other amino acids, consistent with the proposed involvement of D2 in these processes.
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PMID:Expression of mRNA (D2) encoding a protein involved in amino acid transport in S3 proximal tubule. 148 85

The intestine is a major site of expression of the human GLUT5 hexose transporter, which is thought to be localized exclusively to the brush border membrane (BBM) where its major role is likely to be in the absorption of fructose. In this study we present novel biochemical and morphological evidence showing that the GLUT5 transporter is also expressed in the basolateral membrane (BLM) of the human intestine. BBM and BLM were isolated by fractionation of human jejunum. BBM were enriched with alkaline phosphatase activity by over 9-fold relative to a crude jejunal homogenate and contained immunoreactive sucrase-isomaltase and GLUT5 proteins. By contrast the BBM fraction was substantially depleted of immunoreactive a1 subunits of the Na,K-ATPase and GLUT2 glucose transporters which were abundantly present in the BLM fraction. This BLM fraction was enriched by over 11-fold in potassium-stimulated phosphatase activity relative to the crude homogenate; BLM also reacted to immunological probes for GLUT5 but showed no observable reactivity with antibodies directed against sucrase-isomaltase. Quantitative immunoblotting revealed that the BBM and BLM contained near equal amounts of GLUT5 per mg of membrane protein. Immunogold localization of GLUT5 on ultrathin sections of human jejunum showed that GLUT5 was present in both apical BBM and BLM. This gold labelling was absent when antiserum was pre-incubated with the antigenic peptide corresponding to a specific C-terminal sequence of human GLUT5. Quantitative analyses of the number of gold particles per unit length of BBM and BLM indicated that the mean density of gold labelling was marginally greater in the BBM (0.399 gold particles/micrometer) than in the BLM (0.293 gold particle/micrometer). The localization of GLUT5 in the BLM of the human jejunum may suggest that it specifically participates in the transfer of fructose across the basal membrane of the enterocyte.
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PMID:The GLUT5 hexose transporter is also localized to the basolateral membrane of the human jejunum. 761 85

GLUT2 expression is strongly decreased in glucose-unresponsive pancreatic beta cells of diabetic rodents. This decreased expression is due to circulating factors distinct from insulin or glucose. Here we evaluated the effect of palmitic acid and the synthetic glucocorticoid dexamethasone on GLUT2 expression by in vitro cultured rat pancreatic islets. Palmitic acid induced a 40% decrease in GLUT2 mRNA levels with, however, no consistent effect on protein expression. Dexamethasone, in contrast, had no effect on GLUT2 mRNA, but decreased GLUT2 protein by about 65%. The effect of dexamethasone was more pronounced at high glucose concentrations and was inhibited by the glucocorticoid antagonist RU-486. Biosynthetic labeling experiments revealed that GLUT2 translation rate was only minimally affected by dexamethasone, but that its half-life was decreased by 50%, indicating that glucocorticoids activated a posttranslational degradation mechanism. This degradation mechanism was not affecting all membrane proteins, since the alpha subunit of the Na+/K+-ATPase was unaffected. Glucose-induced insulin secretion was strongly decreased by treatment with palmitic acid and/or dexamethasone. The insulin content was decreased ( approximately 55 percent) in the presence of palmitic acid, but increased ( approximately 180%) in the presence of dexamethasone. We conclude that a combination of elevated fatty acids and glucocorticoids can induce two common features observed in diabetic beta cells, decreased GLUT2 expression, and loss of glucose-induced insulin secretion.
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PMID:Dexamethasone induces posttranslational degradation of GLUT2 and inhibition of insulin secretion in isolated pancreatic beta cells. Comparison with the effects of fatty acids. 901 57

Renal tubular reabsorption of glucose is substantially increased in humans and rats with diabetes mellitus. The influx of luminal glucose is mediated by Na+/glucose cotransporter system and glucose efflux from tubules to interstitium by facilitative glucose transporters (GLUT). In Zucker diabetic rats, GLUT2 protein levels of renal proximal tubules were higher than in control litter mates: 9.67 +/- 1.95 versus 4.72 +/- 1.55 (P = 0.0073). In the same proximal tubules, diabetes was associated with minor decreases in GLUT1 protein levels: 1.96 +/- 0.37 for diabetics and 2.37 +/- 0.34 for controls (P = 0.12). Na+/glucose cotransporter system protein levels were similar in both groups, whereas Na+/K+ ATPase levels were slightly decreased in diabetic rats, but the difference was not statistically significant. In this report, it is suggested that in long-term uncontrolled diabetes, GLUT2 transporters are overexpressed in renal tubules. This adaptation promotes low-affinity, high-capacity glucose efflux. The higher number of high K(m) GLUT2 ensures that glucose reabsorption is increased by promoting glucose efflux, which could be rate-limiting in the face of hyperglycemia.
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PMID:Overexpression of GLUT2 gene in renal proximal tubules of diabetic Zucker rats. 918 62

All-trans retinyl palmitate (RP) (1000 IU/kg body weight) was orally administered to rats for three days. The absorption of 3-O-methyl-D-glucose (3-OMG), which is actively transported by Na+-dependent D-glucose co-transporter (SGLT1), in the small intestine of the control and RP-treated rats was investigated by the in vito everted sac and in situ closed loop of intestine techniques. The absorption of [3H]3-OMG in both experiments of the in vito everted sac and in situ closed loop of intestine significantly increased in the RP-treated rats. AUC(0-120min) obtained from the [3H]3-OMG plasma concentration vs. time curve in the RP-treated rats was significantly larger than that in the control rats. On the other hand, the activity of Na+-K+-adenosinetriphosphatase (ATPase) and the transport rate of D-glucose mediated by Na+-independent facilitative glucose transporter (GLUT2) on the basolateral membrane (BLM) were similar between the control and RP-treated rats. Thus it is suggested that RP treatment of rats enhance the small intestinal absorption of glucose mediated by SGLT1.
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PMID:Enhanced absorption of 3-O-methyl-D-glucose through the small intestine of rats administered retinyl palmitate. 1158 62

Glucose-6-phosphatase (G6Pase) is a multiple protein complex in the endoplasmic reticulum (ER) that includes a mechanism (known as T3) for glucose exit from the ER to the cytosol. The molecular identity of T3 is not known. T3 has been shown to be functional in the absence of GLUT2, indicating that it is not GLUT2. Here we found a 55-kDa protein in high-density microsomal fraction (HDM) of rat hepatocytes that is recognized by polyclonal GLUT2 antibody raised against the GLUT2 C-terminal 14-amino-acid-sequence peptide. HDM contained calnexin but no integrin-beta1 or Na/K ATPase in Western blotting. Significant GLUT2 immunoreactivity was colocalized with colligin, an ER marker, in confocal microscopy. Furthermore, the 55-kDa protein in HDM was labeled with a covalently reactive, impermeable glucose transporter substrate, 1,3-bis-(3-deoxy-D-glucopyranose-3-yloxy)-2-propyl 4-benzoyl-benzoate (B3GL) when hepatocyte homogenates, but not intact cells, were labeled. In addition glucose efflux from HDM vesicles was sensitive to B3GL treatment in a dose-dependent manner. Based on these findings, we suggest that T3 may be a novel facilitative glucose transporter that is highly homologous to GLUT2 in the C-terminal sequence, thus cross-reacting with the GLUT2 antibody. The finding will be useful in molecular identification and cloning of T3.
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PMID:The hepatocyte glucose-6-phosphatase subcomponent T3: its relationship to GLUT2. 1210 Oct 13

The ability of the intestine to adapt to changes in environmental stimuli may be compromised with aging. Young animals fed saturated fatty acids (SFA) versus polyunsaturated fatty acids (PUFA) have an increased intestinal uptake of glucose. The objectives of this study were to determine (1) the effects of age on glucose uptake in rats; (2) the influence of feeding SFA versus PUFA; and (3) the mechanisms of these age- and diet-associated changes. Male Fischer 344 rats aged 1, 9 and 24 months received semi-purified isocaloric diets enriched with either SFA or PUFA. The uptake of 14C-labelled D-glucose was determined in vitro using the intestinal sheet method. Northern blotting, Western blotting and immunohistochemistry were used to determine the effects of age and diet on SGLT1, GLUT2 and Na(+)K(+)-ATPase. The mucosal surface area of the jejunum was reduced in 9 and 24 as compared with 1-month-old rats fed SFA. PUFA delayed this age-associated reduction in surface area. In SFA, the ileal uptake of glucose fell with age when expressed on the basis of intestinal or mucosal weight. Feeding PUFA prevented this decline. Alterations in glucose uptake were not paralleled by the changes in SGLT1, GLUT2 or Na(+)K(+)-ATPase abundance.
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PMID:Feeding a polyunsaturated fatty acid diet prevents the age-associated decline in glucose uptake observed in rats fed a saturated diet. 1273 4

Studies performed using human and animal models offer conflicting results regarding the effect of age on nutrient absorption. The objectives of this study were to determine (1) the effects of aging on the in vitro uptake of glucose in rats; and (2) the molecular mechanisms of these age-associated changes. Male Fischer 344 rats aged 1, 9 and 24 months were fed a standard laboratory diet (PMI # 5001). The uptake of 14C-labelled D-glucose was determined in vitro using the intestinal sheet method. Northern blotting, Western blotting and immunohistochemistry were used to determine the effects of age on the BBM sodium-dependent glucose transporter, SGLT1, and the BLM Na+K(+)-ATPase. When expressed on the basis of intestinal weight, mucosal weight or surface area, there was a reduction in glucose uptake in the 24-month-old animals. SGLT1, GLUT2 and Na+K(+)-ATPase mRNA and protein abundance did not parallel the changes seen in glucose uptake. These results indicate that (1) age reduces in vitro intestinal glucose uptake in the rat; and (2) this age-associated decline in glucose uptake was not explained by alterations in SGLT1, GLUT2 or Na+K(+)-ATPase.
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PMID:The age-associated decline in the intestinal uptake of glucose is not accompanied by changes in the mRNA or protein abundance of SGLT1. 1465 92

Mice lacking the mesenchymal winged helix transcription factor Foxl1 exhibit markedly abnormal small intestinal epithelia and postnatal growth retardation. We investigated whether defects in intestinal nutrient uptake and specific transport processes exist in mice homozygous for a Foxl1 null allele (Foxl1-/-). Foxl1-/- mice and controls on a defined genetic background were weighed regularly and killed at 2, 4, and 12 wk of age. Intestinal uptake studies, quantitative real-time PCR, RNase protection assays, and Western blot analyses were performed. Foxl1-/- mice have dysmorphic small intestinal epithelia and postnatal growth retardation. Foxl1-/- mice demonstrate decreased small intestinal uptake of D-glucose in all age groups studied. Intestinal uptake of D-fructose and two amino acids, L-proline and L-leucine, is not altered. Consistent with these findings, Foxl1-/- mice show decreased levels of the intestinal D-glucose transporter SGLT1. Expression of sucrase-isomaltase, lactase, GLUT2, and Na+-K+ ATPase are not changed. Foxl1-/- mice demonstrate markedly abnormal intestinal epithelia, postnatal growth retardation, and decreased intestinal uptake of D-glucose. The specific effect of Foxl1 on intestinal d-glucose uptake is due to decreased production of SGLT1 protein in the small intestine. Thus we identified, for the first time, a link between a mesenchymal factor, Foxl1, and the regulation of a specific epithelial transport process.
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PMID:Foxl1 null mice have abnormal intestinal epithelia, postnatal growth retardation, and defective intestinal glucose uptake. 1515 78

Intestinal function in young animals is influenced by maternal factors, such as alterations in the maternal diet. Glucagon-like peptide 2 (GLP-2) enhances intestinal growth and absorption in mature animals. Glucocorticosteroids induce intestinal maturation in neonates and increase sugar uptake in adult animals. It is not known if maternally administered GLP-2 or glucocorticosteroids have persistent effects on intestinal transport in the offspring. This study was undertaken to determine (1) the influence of maternal GLP-2, dexamethasone (DEX) and GLP-2+DEX on intestinal sugar uptake in postweaning offspring and (2) if alterations in uptake are due to variations in intestinal morphology, sugar transporter abundance or the abundance of selected signals. Nursing rat dams were treated during pregnancy and lactation with GLP-2 (0.1 mug/g per day sc), DEX (0.128 microg/g per day sc), GLP-2+DEX or placebo. The offspring were sacrificed 4 weeks after weaning, and glucose and fructose uptake was determined using an in vitro intestinal ring uptake technique. sodium-dependent glucose transporter, glucose transporter (GLUT) 5, GLUT2, sodium potassium adenosine triphosphatase and selected signals were assessed by immunohistochemistry. The treatments did not affect body weights or intestinal morphology. GLP-2 and GLP-2+DEX increased jejunal fructose uptake, and GLP-2+DEX increased the jejunal and ileal maximal transport rate for glucose uptake. Protein kinase B and mammalian target of rapamycin abundance were also increased, while transporter abundance was unchanged. We speculate that these alterations in sugar uptake may be due to changes in the intrinsic activity of the transporters mediated by the phosphatidylinositol-3-kinase pathway. These alterations in uptake may have nutritional implications for the offspring of mothers who may be treated with GLP-2 or glucocorticosteroids.
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PMID:Dexamethasone and GLP-2 administered to rat dams during pregnancy and lactation have late effects on intestinal sugar transport in their postweaning offspring. 1765 62


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