Dietary regulation of the intestinal sodium-dependent glucose cotransporter (SGLT1).
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Biomedical subjects
Publications and source records attributed to D Scott.
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Growing lambs were fed diets that just met their requirement for Ca but which supplied either 1 or 3 times their requirement for P and the effects on Ca and P retention and on bone turnover were monitored. Feeding the high P diet had no adverse effect on Ca and P absorption or retention or on bone formation rate. Bone resorption rate was a little higher in lambs fed the high P diet but there were no differences between treatments in plasma parathyroid hormone, 1,25-dihydroxyvitamin D3 or 25-hydroxyvitamin D3 levels or in bone mineral content. It would appear from these results that feeding diets that are rich in P is unlikely to have any adverse effect on skeletal mineralization in the lamb provided that their minimum requirement for Ca is met.
Growing lambs were fed diets either low or adequate in phosphorus and their effects on Ca and P retention, bone formation and resorption and on ruminal microbial protein synthesis were measured. Plasma osteocalcin was used as an indicator of bone formation rate. Levels in plasma were lower in lambs fed the low P diet and were associated with a fall in plasma P concentration and reduced Ca and P retention. Low P intake had no effect on microbial protein synthesis or on bone resorption determined using urinary pyridinoline and deoxypyridinoline as markers. These results suggest that lack of mineral, rather than reduced ruminal microbial protein synthesis, is the main factor contributing to the reduction in bone formation rate seen in lambs fed low P diets.
The mouth-to-caecum transit time of food was measured using the rise in breath hydrogen after a standard breakfast of baked beans on two occasions in seven healthy volunteers. The first occasion was after resting and the second after moderate exercise on a bicycle ergometer. There was no significant difference between the transit times with or without prior exercise. It is concluded that moderate exercise taken before food does not interfere with transit time and therefore should not in that way interfere with nutrition.
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The extent of cell cycle delay of lymphocytes X-irradiated in G2 phase was measured by mitotic inhibition determinations in 66 controls, 14 ataxia-telangiectasia (A-T) homozygotes and 27 obligate heterozygotes. Homozygotes had a significantly reduced mitotic index (MI) in unirradiated samples and showed significantly less radiation-induced mitotic inhibition than controls. This confirms our earlier disputed observations on A-T fibroblasts and demonstrates a G2 check-point defect in addition to the well-known defects in S phase and at the G1-S phase transition. There are two separate and opposite abnormal G2 responses of A-T cells; a primary event in which cells in G2 at the time of irradiation suffer less delay than controls, and a secondary event in which cells irradiated at earlier stages of the cycle are more delayed when they pass into G2. The MI of unirradiated heterozygote cells and the extent of mitotic inhibition were indistinguishable from controls. Spontaneous unstable chromosome aberrations were, as previously reported, significantly higher in homozygotes than in controls. This was true for breaks, but not for gaps. There was a suggestion of an increase in breaks in heterozygotes, but a much larger study would be required to confirm or refute this.
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AIMS: To investigate the costs and mortality associated with admission for diabetic foot problems. METHODS: Identification of patients by codes for diabetes and peripheral vascular disease from routinely collected hospital discharge data. Information was collected retrospectively from charts. Post discharge outcome was assessed by discussion with general practitioners. RESULTS: 357 patients accounted for 503 admissions. 11-15% of patients (n = 49) were admitted for diabetic foot problems. Patients with type 1 diabetes had shorter lengths of stay than those with type 2 diabetes, were more likely to be admitted with chronic renal failure and less likely to be admitted with ischaemic heart disease. Maori and Pacific Island patients with type 2 diabetes were admitted at a younger age than Europeans (53 (SD12) vs 56 (11) vs 69 (13) years respectively, p < 0.001). Admissions for diabetic foot problems resulted in the longest hospital stay in comparison with other causes (19 (1-184) days vs 8 (1-116)) days. Average cost per diabetic foot admission was $12,500 with a total annual cost of over $600,000. CONCLUSION: The diabetic foot is expensive and yet these costs are largely avoidable with improvement in patient education, motivation, monitoring and earlier intervention. It would be better to have in place improved community and hospital care before the predicted growth in the diabetic population associated with ageing.
We have investigated the mechanisms of regulation of the Na+/glucose co-transporter (SGLT1) in a ruminant animal, which is an exceptional model system for studying intestinal glucose transport. Pre-ruminant lambs absorb glucose, produced by hydrolysis of the milk sugar lactose, in the intestine via apical SGLT1 and basolateral facilitative glucose transporters (GLUT2). Weaning coincides with the development of the rumen, and consequently the amount of hexoses reaching the small intestine of the ruminant sheep is undetectable. During development, SGLT1 activity and abundance in intestinal brush-border membranes decreased by over 200-fold, and either maintaining lambs on a milk replacer diet or infusing sheep intestine with D-glucose restored co-transporter activity and expression. We have measured ovine intestinal SGLT1 mRNA levels during development, with changes in diet and after direct infusion of D-glucose or methyl alpha-D-glucopyranoside into the intestinal lumen, in order to determine the level of regulation. During development, mRNA levels decreased only 4-fold. Lambs maintained on a milk replacer diet showed no change in mRNA levels relative to age-matched controls. Finally, upon infusion of the intestine of the ruminant sheep with sugars, D-glucose infusion increased SGLT1 mRNA, but only by 2-fold, compared with a 60-90-fold increase in co-transporter number and activity. Since the change in Na(+)-dependent glucose transport activity is correlated with SGLT1 protein abundance, and since changes in mRNA levels do not account for the dramatic changes in protein abundance, we conclude that the principal level of SGLT1 regulation by luminal sugar is translational or post-translational.
From more than 500 tumours reported in human primary immune deficiencies a majority has been observed in two disorders: ataxia telangiectasia (A-T) and common variable immune deficiency (CVID). Since both diseases have an increased risk of lymphomas/leukaemias and gastrointestinal tumours, suggesting a common risk factor, and the cells derived from A-T patients exhibit an increased chromosomal radiosensitivity we analysed chromosome damage in the G2 lymphocytes of 24 CVID patients and 21 controls after X-irradiation in vitro. There was a significant difference in mean aberration yields between patients and controls. Three CVID patients had yields higher than the mean + 3SD of the controls. Six patients but only one control had yields higher than the mean + 2SD of controls. The patient with the highest chromosomal radiosensitivity subsequently developed a lymphoma. Repeat assays on the same blood sample, with a 24-h delay in setting up the second culture, showed as much variability for control donors as the variation between control donors although for CVID patients inter-individual variation was greater than the difference between results of repeat samples. There was a weak positive correlation between radiosensitivity and age of donor. Chromosomal radiosensitivity of five patients with X-linked hypogammaglobulinaemia was not different from healthy donors. The mean mitotic index (MI) for unirradiated samples from CVID patients was significantly lower than for controls and there was an inverse relationship between MI and aberration yields in the patients, but not in controls. We suggest that the defect in CVID patients that reduces response to mitogenic stimuli may have mechanism(s) in common with those involved in cellular repair processes.
A new medical instrument is presented that produces a doppler blood flow image from a laser beam in a raster pattern and the results of a pilot study which shows this technique to be highly accurate in assessing burn depth is described.
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