Renal disease leads to perturbations in calcium and phosphate homeostasis and vitamin D metabolism. Dietary fructose aggravates chronic kidney disease (CKD), but whether it also worsens CKD-induced derangements in calcium and phosphate homeostasis is unknown. Here, we fed rats diets containing 60% glucose or fructose for 1 mo beginning 6 wk after 5/6 nephrectomy or sham operation. Nephrectomized rats had markedly greater kidney weight, blood urea nitrogen, and serum levels of creatinine, phosphate, and calcium-phosphate product; dietary fructose significantly exacerbated all of these outcomes. Expression and activity of intestinal phosphate transporter, which did not change after nephrectomy or dietary fructose, did not correlate with hyperphosphatemia in 5/6-nephrectomized rats. Intestinal transport of calcium, however, decreased with dietary fructose, probably because of fructosemediated downregulation of calbindin 9k. Serum calcium levels, however, were unaffected by nephrectomy and diet. Finally, only 5/6-nephrectomized rats that received dietary fructose demonstrated marked reductions in 25-hydroxyvitamin D 3 and 1,25-dihydroxyvitamin D 3 levels, despite upregulation of 1␣-hydroxylase. In summary, excess dietary fructose inhibits intestinal calcium absorption, induces marked vitamin D insufficiency in CKD, and exacerbates other classical symptoms of the disease. Future studies should evaluate the relevance of monitoring fructose consumption in patients with CKD.

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Energy levels in enterocytes may play a role in NaPi-2b inhibition by luminal fructose. Consumption of fructose that supplies approximately 10% of caloric intake by Americans clearly affects absorption of Pi and may promote Pi homeostasis in patients with impaired renal function.

Lifelong caloric restriction increases median and maximum life span and retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, does lifelong caloric restriction induce adaptations in intestinal nutrient transport? We initially compared intestinal transport of sugars and amino acids between 24-mo-old mice allowed free access to food [ad libitum (AL)] and those provided a calorically restricted [40% less than ad libitum (CR)] diet since 3 mo of age. We found that CR mice had significantly greater transport rates for D-glucose, D-fructose, and several amino acids and had significantly lower villus heights. Total intestinal absorptive capacities for D-glucose, D-fructose, and L-proline were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight 0.75) was approximately 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously published results in young AL mice suggests that caloric restriction delays age-related decreases in nutrient transport. In contrast to published studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter. We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on intestinal nutrient transport, intestinal mass, and total absorptive capacity. Thus chronic but not short-term caloric restriction increases intestinal nutrient transport rates in aged mice, and the main mechanism underlying these increases is enhanced transport rates per unit intestinal tissue weight.

Thiamin transport in human erythrocytes and resealed pink ghosts was evaluated by incubating both preparations at 37 or 20 degrees C in the presence of [3H]-thiamin of high specific activity. The rate of uptake was consistently higher in erythrocytes than in ghosts. In both preparations, the time course of uptake was independent from the presence of Na+ and did not reach equilibrium after 60 min incubation. At concentrations below 0.5 microM and at 37 degrees C, thiamin was taken up predominantly by a saturable mechanism in both erythrocytes and ghosts. Apparent kinetic constants were: for erythrocytes, Km = 0.12, 0.11 and 0.10 microM and Jmax = 0.01, 0.02 and 0.03 pmol.microliter-1 intracellular water after 3, 15, and 30 min incubation times, respectively; for ghosts, Km = 0.16 and 0.51 microM and Jmax = 0.01 and 0.04 pmol.microliter-1 intracellular water after 15 and 30 min incubation times, respectively. At 20 degrees C, the saturable component disappeared in both preparations. Erythrocyte thiamin transport was not influenced by the presence of D-glucose or metabolic inhibitors. In both preparations, thiamin transport was inhibited competitively by unlabeled thiamin, pyrithiamin, amprolium and, to a lesser extent, oxythiamin, the inhibiting effect being always more marked in erythrocytes than in ghosts. Only approximately 20% of the thiamin taken up by erythrocytes was protein- (probably membrane-) bound. A similar proportion was esterified to thiamin pyrophosphate. Separate experiments using valinomycin and SCN- showed that the transport of thiamin, which is a cation at pH 7.4, is unaffected by changes in membrane potential in both preparations.

A 9-year study of thiamine metabolism and cellular transport was performed in two patients with thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and sensorineural deafness, in their relatives, and in age-matched controls from the same area. The ratios between the content of thiamine and that of its phosphoesters in erythrocytes were within the normal range, whereas the absolute values of thiamine and thiamine compounds were reduced by about 40% as compared to controls. Thiamine pyrophosphokinase activity was about 30% lower than in controls. Thiamine treatment restored the levels of thiamine and thiamine compounds to normal values, whereas kinase was unaffected. Both the saturable (specific, predominant at low, less than 2 mumol/L, physiological concentrations of thiamine) and the non-saturable component of thiamine transport were investigated. Erythrocytes and ghosts from patients exhibited no saturable component, this abnormality being specific for the patients and not shared by their parents. It is concluded that the cells from thiamine-responsive megaloblastic anaemia patients contain low levels of thiamine compounds, probably due to their inability to take up and retain physiological concentrations of thiamine, as a result of the lack of the saturable, specific component of transport and reduced thiamine pyrophosphokinase.

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The rate of intestinal absorption of sugars and their site of absorption determine postprandial plasma glucose concentrations. Does chronic consumption of high-carbohydrate, high-fiber, low-fat diets of the type recommended by many diabetes associations induce adaptive changes in transport and metabolism of sugars in the small intestine? Control and STZ-induced diabetic (> 60 days diabetic) mice were fed high-carbohydrate or no-carbohydrate rations for 7 days. Brush-border glucose and fructose uptake per milligram increased 2 times with dietary carbohydrate in both diabetic and control mice; uptake, however, did not differ between diabetic and control mice. Compared with the distal small intestine, glucose uptake per milligram was 2 to 6 times higher in the proximal and middle regions, and enhancement of uptake by diet was limited to these regions. Changes in site density of intestinal glucose transporters as determined by specific phlorizin binding were tightly correlated with changes in brush-border glucose uptake per milligram. There were neither diabetes- nor diet-induced changes in the Kd of specific phlorizin binding, in the amount of glucose absorbed per transporting site, or in passive glucose permeability. Intestinal weights, wt/cm, intestinal length, and mucosal mass increased significantly with diabetes, and sugar transport per centimeter and per small intestine was up to 60% greater in diabetic mice. Dietary carbohydrate stimulated specific sucrase activity in the proximal small intestine of both diabetic and control mice. Chronic diabetes enhances sugar transport by nonspecific increases in intestinal mass.(ABSTRACT TRUNCATED AT 250 WORDS)