Understanding vitamin DPregnant and virgin control rats testosteron mann alter your fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation. Bone mineral density, content, and mechanical strength each decreased with lactation, vitamin d and glucose transport then fructose exacerbated these effects. Dietary bitamin inhibits lactation-induced adaptations in rat 1, OH 2 D 3 synthesis and calcium transport. In humans, defects in the development of the newborn skeleton are associated with maternal vitamin D deficiency 5. Vitamin d and glucose transport, the nephrectomized rats were also hyperphosphatemic and hypercalcemic. We then show that fructose specifically prevents lactation-induced increases in TRPV5 and 6, as well as CaBP9k and 28k expression in the duodenum and the kidney, respectively. Rats were kept under standard conditions:
Pregnant and virgin control rats were fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation. Bone mineral density, content, and mechanical strength each decreased with lactation, but then fructose exacerbated these effects. Dietary fructose inhibits lactation-induced adaptations in rat 1, OH 2 D 3 synthesis and calcium transport.
In humans, defects in the development of the newborn skeleton are associated with maternal vitamin D deficiency 5. However, the nephrectomized rats were also hyperphosphatemic and hypercalcemic. We then show that fructose specifically prevents lactation-induced increases in TRPV5 and 6, as well as CaBP9k and 28k expression in the duodenum and the kidney, respectively.
Rats were kept under standard conditions: These isocaloric diets are designed to meet the nutrient requirements of gestation and lactation in rodents. Animals were fed the high-carbohydrate diets ad libitum for 6 wk from d 2 of gestation until the end of lactation, which corresponded to d 21 after birth.
Blood sampling from the tail vein was done on d 21 of lactation prior to removal of pups. Same-age virgin controls were also sampled on the same days Supplemental Fig. In the intestinal regional compensation experiment, tissues were also taken from the jejunum. The outer luminal and inner serosal compartments had equal initial concentrations 0. Four 1-cm jejunal segments were made into everted sleeves, mounted on rods, and preincubated for 5 min in Krebs-Ringer bicarbonate KRB , as described previously Two segments each were then incubated in 50 mM glucose or fructose KRB solutions containing tracer concentrations of 14 C-glucose or 14 C-fructose, respectively.
Intestinal P i transport was determined in two consecutive 4-cm segments of medial jejunum using the previously described everted gut sac assay Briefly, serum samples were delipidated, and 1, OH 2 D 3 was immunoextracted before the assay.
The control group was the virgin rats fed starch. Primers for the following genes are forward; reverse; annealing temperature: All images of sections being compared were obtained with the same settings of the microscope. Nonspecific staining with secondary antibodies only was consistently negligible. After being thawed, samples were prepared for immunoprecipitation, as described previously Primers for ChIP were designed using Primer3 http: Regions within — bp from the cis element of nuclear receptors are able to detect binding as previously shown After whole-body measurements, the left and right femora were dissected, and muscle fibers were removed.
The right femur was used for bone mechanical testing, as described previously Polar moment of inertia about the centroidal axis, represented by the longitudinal axis of the bone , torque to failure, structural stiffness, and ultimate shear stress were obtained through standard equations, modeling each femur as a hollow ellipse.
Throughout gestation, food intake was the same in all 6 groups Supplemental Fig. Since diet had no effect on feeding rate, differences in caloric intake did not confound results. Dietary carbohydrate had no significant effect on body weight. Data in panels A and B were normalized to levels in virgins fed S.
Data were normalized to levels in virgin rats fed S. Lactation also had no effect on fructose uptake Fig. Effects of dietary sugars on intestinal glucose and fructose uptake in lactating and virgin rats. Bars, analyses, and normalization as in Fig.
We also examined P i as it is critical for bone formation. Active transepithelial P i transport in the jejunum was almost nonexistent in virgins Fig. Effects of dietary sugars on intestinal P i absorption in lactating and virgin rats.
Because of the low rates of active P i transport in adult rats 44 , which fluctuated around 0, we could not express rates relative to virgin rats. In contrast, lactation and diet had no effect on serum levels of Pi. Serum fructose levels varied with diet, but not lactation, as fructose consumption increased blood fructose levels in both dams and virgins. For serum glucose levels, there was a significant interaction between diet and maternal status, suggesting that the response to diet may depend on whether the rats were lactating.
Fructose effects on blood chemistry: Means with different superscript letters are significantly different. There is a dramatic decrease in levels of 1, OH 2 D 3 in dams fed fructose compared to those fed glucose or starch. By in silico screening, we located the putative VDREs in the promoter regions of both genes in rats Fig. Relative mRNA levels were then normalized to those of dams fed starch. Sonication of our samples generated DNA fragments of — bp. Because primers within — bp from the cis element of nuclear receptors are able to detect binding 15 , primers designed as indicated in panel B should allow us to detect VDR interactions with the promoter regions of interest.
ChIP signals were normalized to input signals. Only one band appears with the primer sets used Supplemental Fig. VDR binding to the promoter of CaBP9k was also highly dependent on diet but did not vary among the different promoter regions examined.
ChIP assays were performed using anti-acetylated histone H4 antibody in the small intestine of lactating dams fed glucose, fructose, or starch diet for 6 wk. We examined the effects of fructose on the kidney since it is the major organ system involved in 1, OH 2 D 3 synthesis that decreases with fructose.
The renal somatic index varied with lactation and with diet Fig. Despite the hypertrophy of the kidney Fig. Effect of diet on the kidney morphology of lactating dam and virgin rats. Kidneys were obtained from dams D or virgin V rats fed a glucose G , fructose F , or starch S diet for 6 wk. A Kidney somatic index. B Hematoxylin-and-eosin staining of a transverse section at the longest point of the right kidney of a rat representing each diet group.
Length horizontal arrow with grid and width vertical arrow of the VS kidney were determined initially, and then the same-sized arrows superimposed on the sections were obtained from DG, DF, DS, VG, and VF rats, to depict differences in size.
Results indicate that the representative, randomly chosen VS kidney is smaller than those of dams, particularly that of dams fed fructose. In the renal cortical area of kidneys from dams fed glucose or starch, CYP27B1 expression is higher in the proximal tubules Fig. In dams fed fructose Fig. Effect of diet on renal enzymes involved in the synthesis and degradation of 1, OH 2 D 3 in lactating and virgin rats. Kidney homogenates were obtained from dams D and virgin rats fed a glucose G , fructose F , or starch S diet for 6 wk.
In dams fed fructose panel DF , distal tubular and glomerular cells also have low abundance of CYP27B1, and there is reduced expression dotted yellow arrows of CYP27B1 in the proximal tubule. CYP27B1 immunolocalization for virgin rats is not shown since no effect of dietary fructose was observed see panel A.
All data were normalized to levels in virgins fed S. GLUT5 was expressed mainly in the proximal straight tubule, as was also shown by Ebert et al. The physiological demands of lactation may have been met by compromising bone quality and mechanical properties. It is not clear why dams fed glucose also decreased in BMD as with dams fed fructose.
Similar results were observed for the isolated whole femur, a mainly cortical bone, and for the femoral neck, a more trabecular area.
Lactation and fructose effects on mineral content and mechanical properties of femora from dams and virgin rats fed high levels of glucose, fructose, or starch. Biomechanical testing was then used to assess the structural properties of the femur Table 2. Femurs from dams had significantly reduced stiffness indices compared to those of the virgins.
There were also lactation-related decreases in shear stress and shear modulus but not in torsional rigidity. Because of large blood or tissue requirements for hormonal and transport assays, not all analyses could be done in the same animal; hence, we plotted average instead of individual values to one another.
Regression coefficients and significance P are in boxes. Nevertheless, lactating VDR -null mice still induced TRPV6 expression even if the level of expression of this gene was lower than that of lactating wild-type mice 2 , suggesting a modest regulatory role by other hormones. In our study, however, CaBP9k is modestly expressed in the kidney and is not affected by maternal status or diet Supplemental Fig.
Moreover, CYP24A1 remained unchanged among the three diets, suggesting that degradation rate via hydroxylase did not change with diet. Other studies have shown that reductions in calcitriol concentrations in rats were driven also by reductions in synthesis and not degradation rates Our data show instead a strong positive correlation between CYP27B1 expression and 1, OH 2 D 3 levels, indicating that this negative feedback loop is not working.
Thus, in our model of lactating rats, the fructose-induced increase in PTH concentrations is incongruent with the fructose-induced decrease in 1, OH 2 D 3. Thus, dietary fructose appears to perturb the regulation of renal vitamin D synthesis dashed line. Among the obvious candidates are the phosphaturic compound fibroblast growth factor 23 FGF; ref. S5 and others 35 have shown that dietary fructose induces a robust increase in renal GLUT5 expression. Because postprandial fructose tends to accumulate in the kidney 36 , this increase in serum fructose levels associated with a marked increase in GLUT5 in the kidney raises a question about the potential direct role of GLUT5 in mediating the effect of fructose on renal 1, OH 2 D 3 synthesis.
Lactation is already associated with a decrease in BMC, BMD, and bone mechanical strength, as the skeleton acts as a ready reservoir from which minerals can be mobilized rapidly. Overconsumption of rapidly metabolized sugars may exacerbate the effect of lactation on bone health.
Dietary sucrose has been shown to reduce the mechanical strength and BMC of rat bones 37 , 38 , and excessive consumption of soft drinks laden with sugars may decrease BMD in humans 39 , However, the mechanisms underlying the detrimental effect of sugars on bone remain completely unexplored. Although in this study, glucose feeding was not associated with any perturbation in mineral transport nor in any change in PTH level, there may be other factors involved that affect BMD.
Hyperglycemia, type 2 diabetes, and even a prediabetic state are associated with weaker bones In our study, the rats fed glucose during lactation had normal fasting serum levels of glucose but because of the high levels of glucose in the diet, have likely undergone transient daily postprandial increases in serum levels of insulin that have been recently shown to promote bone resorption There has been a dramatic surge in the United States in per capita consumption of high-fructose corn syrup HFCS , from 0.
When consumption of HFCS is pooled with that of other fructose sources e. This dramatic increase in dietary fructose consumption is tightly correlated with increased incidence in type II diabetes, hypertension, and obesity
GLUT-3 – Wikipedia
Die Aufnahme von Glucose in Zellen wird über Glucosetransporter GLUT geregelt 1 Gramm Vitamin C und Internationale Einheiten Vitamin E einnahmen. Einfluss von Vitamin D auf β-Zellfunktion und Insulinresistenz . GLUT4-Transporter, wodurch Glukose nicht in die Zelle gelangen kann. ( ) Glucose homeostasis in the nonobese diabetic mouse at the prediabetic stage. In turn, Ca2+ homeostasis and skeletal integrity are regulated by vitamin D, .. Ca2+, sugar, and Pi transporter activity and expression change with lactation and .