Glucose diffusion as a rate-limiting step in glucose absorption.
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Blood Glucose↗
Biomedical subjects
I T Johnson
Publications and source records attributed to I T Johnson.
Polyunsaturated fatty acids of the n - 3 series influence intestinal crypt cell production in rats.
The effects of saturated and polyunsaturated dietary lipids on intestinal mucosal cell proliferation were investigated in rats. Animals were randomly allocated to three groups of 10, and fed fibre-free diets containing lipid in the form of lard, corn oil or fish oil at a level of 80 g/kg. Total energy intake was kept constant by pair-feeding. After 14 days the crypt cell production rates (CCPR) at two sites in the small intestine, one site in the caecum and two sites in the colon were determined by the metaphase arrest technique, together with circulating levels of enteroglucagon and gastrin and parameters of mucosal morphology. Consumption of fish oil led to lower CCPR compared to corn oil at all sampling positions except the caecum (Treatment approximately 50% of control values; P < 0.05). In animals fed lard the CCPR in the small bowel was not significantly different to that of animals fed corn oil but their rates were lower in the colon. Post-prandial enteroglucagon and gastrin levels were lower in animals fed fish oil compared to the other two groups. These results suggest that polyunsaturated fatty acids of the n - 3 series may support a relatively low rate of crypt cell proliferation in some regions of the alimentary tract and might thereby tend to suppress the progression of colorectal neoplasms.
Animals↗
Validation of a simple technique for the detection of abnormal mucosal cell replication in humans.
Abnormal intestinal crypt cell proliferation is considered to be an important early risk marker for colorectal cancer but measurement of the rate and spatial distribution of cell division by histochemical localization of DNA synthesis is labour-intensive and expensive. We developed and evaluated a simpler technique for measurement of these parameters using direct visual analysis of mitotic figures in microdissected crypts. The direct crypt analysis technique was applied to colorectal biopsies from patients with ulcerative colitis or no mucosal abnormality. A characteristic shift of cell division toward the intestinal lumen was detected in patients with ulcerative colitis. The direct method was validated using rats fed diets containing cellulose, or guar gum to stimulate mucosal cell proliferation. The crypt cell proliferation rate (CCPR) was measured by the metaphase-arrest technique and the results were compared with direct crypt analysis. There was a fivefold range of CCPR values at three sampling sites across the dietary groups. An excellent linear correlation between the results by the two techniques was obtained (r = 0.98; P < 0.001). In a second experiment the spatial distribution of dividing cells between five zones in colonic crypts, determined by the new method or by staining with BrdU, was compared. Good agreement was again achieved. Visual analysis of intact crypts is a valid technique for the measurement of crypt cell cytokinetics and it is particularly suited for use in a clinical environment.
Animals↗
The clastogenic effects of isothiocyanates.
Four isothiocyanates (ITCs), three of which are commonly found in the human diet, were tested for the ability to induce chromosome aberrations in an SV40-transformed Indian muntjac cell line. Whilst allyl ITC was found to be inactive the other three (benzyl ITC, phenethyl ITC and phenyl ITC) were found to be significant inducers of chromosome damage in the absence of any metabolic activation. Given that experimental data have demonstrated that ITCs can also protect laboratory animals from the induction of tumours by model carcinogens it is proposed that the presence of ITCs in the human diet may, potentially, have both beneficial and harmful consequences depending on the levels consumed.
Animals↗
Allyl isothiocyanate is selectively toxic to transformed cells of the human colorectal tumour line HT29.
Allyl isothiocyanate, a constituent of mustard and certain vegetables found in the human diet, was tested for cytotoxic and cytostatic effects in HT29 human colon carcinoma cells in vitro. For an exposure time of 24 h, allyl isothiocyanate exhibited a Dq of 0.32 microgram/ml and a D0 of 0.74 micrograms/ml. Following detransformation of the cells by treatment with sodium butyrate or dimethylformamide the cells became more resistant to the cytotoxic effects of allyl isothiocyanate, the Dq increasing to 0.74 microgram/ml and the D0 to 0.96 microgram/ml (with butyrate) or 0.84 microgram/ml (with dimethylformamide). At the Dq value for detransformed cells the survival of the control cells was reduced to 56%. Allyl isothiocyanate was also found to be less cytostatic to the mass growth of detransformed populations in that daily doses of 1.6 micrograms/ml over a week reduced the final number of detransformed cells relative to untreated cultures by < 25% whilst growth of the transformed cultures was reduced by > 60%. Given this increased sensitivity of the cells to allyl isothiocyanate when in the transformed state, it is hypothesized that, when consumed in the human diet, this compound may protect against the development of colorectal cancer by selectively inhibiting the growth of transformed cell clones within the gastrointestinal mucosa.
Butyrates↗
Baked rye products modify cholesterol metabolism and crypt cell proliferation rates in rats.
Young adult male rats were made hypercholesterolemic by feeding cholesterol (+ cholic acid). The effect of rye crispbread on hepatic and plasma cholesterol concentrations, hepatic cholesterol synthesis, small intestinal cell turnover and fecal output was investigated. Diets containing 50 and 75% rye crispbread (g dry wt) were compared with positive control diets of similar gross composition, in which the insoluble component of rye was matched with cellulose and the soluble component with guar gum. A negative control diet containing no non-starch polysaccharide was also included. Cholesterol supplementation was maintained in half the rats on each diet. Rye caused a marked increase in fecal output that was greater than that seen in the positive control groups. However, crypt cell proliferation in the small intestine was less than that seen in the high fiber control groups. Rye reduced total plasma cholesterol concentrations only in those rats that continued to receive the high cholesterol diet. However, whether or not cholesterol was fed, the presence of nonstarch polysaccharide caused a decrease in liver cholesterol concentrations. Rye caused a marked increase in hepatic cholesterol synthesis over both the positive controls and the rats fed a fiber-free diet. This implies that rye causes a loss of cholesterol from the body, probably due to malabsorption of bile acids and cholesterol.
Animals↗
'Determination' of sugar alcohol and Polydextrose absorption in humans by the breath hydrogen (H2) technique: the stoichiometry of hydrogen production and the interaction between carbohydrates assessed in vivo and in vitro.
The production of hydrogen from substrates and substrate mixture of sugar alcohols and Polydextrose was determined, both in vivo using the breath hydrogen test, and in vitro, using human faecal microorganisms in anaerobic culture. One objective was to test a previous assumption that the stoichiometry of hydrogen production from different alternative carbohydrates is similar. Another objective was to discover whether hydrogen responses from mixtures of substrates were simply additive, or whether interactions occurred. The breath tests were performed in a 10 subject x 10 substrate factorial design with substrates and substrate mixtures (5-11 g) administered in 42 g chocolate confectionery. Incorporation of the alternative carbohydrates lactitol (L), Isomalt (I) and Polydextrose (P) into otherwise conventional confectionery increased breath hydrogen production by approximately 112, 73 and 11%/g respectively. There was no interaction between L and I or between P and I, but a combination of L and P approximately doubled the breath hydrogen anticipated from their individual contributions (P < 0.05). Anaerobic cultures showed a sixfold range in the efficiency of converting individual substrates and mixtures to hydrogen gas (0.003-0.018 kJ H2 per kJ carbohydrate). The positive interaction between L and P, and the lack of interaction between L and I, and between P and I, found in vivo were reproduced in vitro. The work showed that interpretation of the hydrogen breath test is confounded by differing stoichiometries for hydrogen production, by interaction between substrates and by an uncertain extent to which small intestinal hydrolysis yielding species with a fermentation stoichiometry that differs from the parent substrate.
Absorption↗
Dietary corn oil and guar gum stimulate intestinal crypt cell proliferation in rats by independent but potentially synergistic mechanisms.
The effects of corn oil, guar gum and cellulose on mucosal proliferation were investigated in rats. Animals were allocated to three groups and fed a fiber-free diet or diets containing 100 g/kg of cellulose or guar gum. Each group was subdivided to receive corn oil at 40 or 80 g/kg. The crypt cell production rate (CCPR) was determined after 28 d. Consumption of guar gum or corn oil led to greater CCPR in the ileum and cecum. In a second experiment, animals were allocated to two groups and fed diets containing either cellulose or guar gum (100 g/kg). Each group was again subdivided to receive either corn oil (80 g/kg) or minimal lipid (linolenic acid, 10 g/kg). The trophic effect of guar gum occurred even in the low lipid-fed group, indicating that guar gum exerts a positive effect on cell turnover independently of any interaction with luminal lipid. However, the highest CCPR occurred in animals fed guar gum and corn oil. Postprandial enteroglucagon and gastrin concentrations were highest in animals fed both guar gum and corn oil. Thus, corn oil and guar gum exert independent trophic effects on the intestinal mucosa. The combination of effects led to a three- to four-fold increase in colon mucosal CCPR.
Animals↗
Physiological properties of resistant starch.
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Adaptation, Physiological↗
Dietary fat intake and plasma lipid levels in adolescents.
The relationship between dietary fat intake and fasting plasma lipid levels was assessed in 35 female and 19 male adolescents recruited from two local education authority schools in Norwich, UK. Dietary intakes were assessed using a 7-day weighed dietary record method, coupled with the collection of duplicate diets. Fat and energy intakes calculated using food composition tables were compared with values obtained by direct analysis of duplicate diets. Fasting plasma lipid levels (total, HDL and LDL cholesterol and triglycerides) were measured and compared with total dietary lipids and fatty acid intakes. The average proportion of energy consumed as fat was higher than is currently considered desirable but lower than previous studies have reported for adults. Mean serum total cholesterol values were 4.2 (SEM 0.1) mmol for females and 4.5 (SEM 0.2) mmol for males; this difference was not statistically significant. In male subjects the dietary fatty acid profiles were significantly correlated with several parameters of plasma lipid status which are thought to be risk factors for coronary heart disease, and in particular with the ratio of total:HDL cholesterol.
Adolescent↗
Physiological effects of retrograded, alpha-amylase-resistant cornstarch in rats.
Retrograded amylose was prepared by gelatinization of high amylose cornstarch, followed by storage at 1 degrees C for 48 h. The insoluble residue, which resisted hydrolysis with porcine amylase, was dried and fed to male Wistar rats for 14 d in powdered semisynthetic diet. Control rats received a similar diet containing sucrose in place of resistant starch. Fecal collections were performed throughout the feeding period. After 14 d the animals were killed. The small intestine and cecum were removed for morphological examination, measurement of small intestinal crypt cell production rate (CCPR) and analysis of luminal carbohydrate content. Blood samples were collected for analysis of cholesterol, glucagon, and enteroglucagon. In the starch-fed rats, fecal bulk and excretion of starch were higher than in the controls, but they declined markedly over the feeding period. Cecal size and contents were also greater in the starch-fed rats, and cecal pH was significantly lower. The CCPR was 66% higher in the ileum of the starch-fed rats (P less than 0.001), but there was no difference in the jejunum. There were no differences in serum cholesterol or enteroglucagon levels. We conclude that retrograded amylose is partially degraded in the alimentary tract of rats, but it contributes significantly to fecal bulk.
Amylose↗
Fermentable carbohydrate reaching the colon after ingestion of oats in humans.
A simulated digestion technique was used to investigate the characteristics of starch hydrolysis in uncooked, cooked and extrusion-cooked oat products in vitro. The rate and extent of starch hydrolysis were both significantly lower in uncooked rolled oats than in the same material after brief boiling or extrusion cooking. A similar degree of maldigestion in vivo would lead to as much as an estimated 68% of oat starch entering the colon. Breath-hydrogen measurements were used to compare the fermentable carbohydrate content of uncooked and briefly boiled rolled oats in human volunteers and to estimate the relative contributions of soluble dietary fiber and undigested starch to the fermented component. Isolated oat gum (beta-glucan) was readily fermented in vivo and was apparently the main fermentable component of cooked rolled oats. Uncooked rolled oats gave a higher excess hydrogen production than cooked oats, but the results were variable and the differences not statistically significant. In an additional experiment, lactulose was used as a fermentable reference material to calculate the apparent fermentable carbohydrate content of rolled oats and oat gum. Uncooked rolled oats were estimated to contain a statistically significant quantity of undigested starch, amounting at most to 1.01 +/- 0.40 g (mean +/- SEM) of undigested starch per 50 g of fresh weight. We concluded that starch hydrolysis in oats is limited to some extent by the physical state of the food matrix, but this effect may be greatly overestimated by simulated digestion procedures in vitro.
Adult↗
Effects of conventional sucrose-based, fructose-based and isomalt-based chocolates on postprandial metabolism in non-insulin-dependent diabetics.
Milk chocolate is rich in both sucrose and fat, and is therefore considered unsuitable for diabetics. Nevertheless there is little information on the metabolic effects of conventional chocolate or specialized formulations with reduced sucrose content. In the present study six male non-insulin-dependent diabetes mellitus patients (age range 35-60 years; body-mass index less than 28) consumed test meals of chocolate (75 g) on three separate occasions. The control chocolate contained sucrose (45.5% w/w); the test chocolates contained either fructose (45.5% w/w) or isomalt (45.1% w/w). The latter is a sweet disaccharide alcohol which has no glycaemic effect when consumed as a pure compound. Venous blood samples were obtained at 30 min intervals for 5 h, and analysed for glucose, insulin, lactate and triglycerides. All three chocolates provoked a sustained rise in blood glucose, which reached a maximum at 90 min after ingestion and returned to baseline values by 5 h. The highest blood glucose levels occurred after conventional chocolate, and differences were statistically significant at 60 and 90 min (P less than 0.05). The area under the glycaemic curve for isomalt chocolate was 36% smaller than that for conventional chocolate (P less than 0.05), and there were differences in insulin and lactate levels, consistent with the lower glycaemic effect. The glycaemic response to the fructose-based chocolate was also lower than that to control chocolate but the difference was not significant. All three chocolates led to a similar sustained rise in serum triglyceride levels. Isomalt appears to be a palatable alternative sweetener capable of reducing the glycaemic effect of diabetic confectionary.
Adult↗
The biological effects and digestible energy value of a sugar-beet fibre preparation in the rat.
A sugar-beet fibre preparation (SBF) was incorporated into a semi-synthetic rat diet at a level of 100 g/kg. The material caused no feed aversion, and gain of live weight was unimpaired. SBF appeared to be slightly more fermentable than wheat bran and only marginally less effective as a faecal bulking agent when compared with equalized intakes of non-starch polysaccharide. SBF did not stimulate mucosal cell turnover in the small intestine. Some enlargement of the caecum was observed in animals given SBF, but it was no greater than that of animals given wheat bran. Animals given SBF had a lower serum cholesterol concentration than both the fibre-free controls and those given wheat bran. This hypocholesterolaemic effect was less than that of guar gum however. The partial digestibility of energy for SBF was 0.64, and its partial digestible energy value was 11.3 kJ (2.7 kcal)/g. The partial digestibility of energy for non-starch polysaccharide in SBF was estimated to be 0.53 and its partial digestible energy value was 9.1 kJ (2.2 kcal)/g. This value was not significantly different from that expected for unavailable carbohydrate in mixed human diets.
Animals↗
Fibre sources for the food industry.
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Anticholesteremic Agents↗
Effect of oat gum on the physical properties of the gastrointestinal contents and on the uptake of D-galactose and cholesterol by rat small intestine in vitro.
Recent reports indicate that oats have a relatively low glycaemic effect in comparison with other carbohydrate food, and that their consumption leads to a reduction in plasma-cholesterol levels in man. These properties may be due to a soluble non-starch polysaccharide in oats. The present study was undertaken to explore the physiological properties of this material. Three groups of male Wistar rats were meal-fed on a control diet free of soluble dietary fibre for 10 d before being given a 10 g meal of either the control diet, a diet containing oat gum (beta-glucan), or finely ground rolled oats. The contents of the stomach, small intestine and caecum were later recovered and the weight, water content and viscosity were measured. The small intestinal contents from oat-gum-fed or oat-fed rats had a higher wet: dry weight ratio than that of the controls, and a higher viscosity. In in vitro studies the rate of uptake of D-galactose by jejunal rings was reduced in the presence of oat gum. The estimated Michaelis-Menten constant for the carrier-mediated component in the presence of oat gum was higher than that for controls, but the maximum transport rates were similar. Cholesterol uptake by everted jejunal sacs was progressively inhibited by increasing concentrations of oat gum in the mucosal medium. It is concluded that increased viscosity of the contents of the small intestine may contribute to the low glycaemic index and hypocholesterolaemic effects of oats in man. Oats appear to be amongst the few palatable sources of viscous dietary fibre in the conventional Western diet.
Animals↗
Can the composition and properties of carbohydrates in manufactured foods be modified to obtain nutritional benefits?
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Carbohydrates↗
The effect of Gypsophila saponins in the diet on mineral status and plasma cholesterol concentration in the rat.
1. Immature, male Wistar rats were allocated to one of six groups and caged individually. The first group was given a semi-synthetic diet containing 38 mg iron and 55 mg zinc/kg (basal group). The second and third groups were given a diet containing 10 mg Zn and 12 mg Fe/kg respectively (low-Zn and low-Fe groups). Groups four, five and six were given similar diets containing 20 g Gypsophila saponins/kg. After 21 d the Fe and Zn status of the rats was estimated and plasma cholesterol concentration determined. 2. Measurements of whole blood haemoglobin concentration, packed cell volume and liver Fe stores indicated that rats in the basal + saponin and low-Fe + saponin groups had a significantly reduced Fe status when compared with their controls. Rats in the low-Zn + saponin group also showed a trend toward reduced Fe stores. 3. Zn status, as judged by femur Zn concentration, was not adversely affected by the inclusion of Gypsophila saponins in the diet. 4. Consumption of the saponins resulted in a significant reduction in blood cholesterol concentration, with rats in both the low-Fe groups having significantly lower concentrations than their basal and low-Zn counterparts. 5. In view of suggestions that the consumption of saponins should be encouraged because of their ability to lower blood cholesterol, possible effects on Fe metabolism should be investigated further, particularly with respect to the levels and sources of saponin in the human diet.
Animals↗