24-25-dihydroxyvitamin-d-3 and Body-Weight

Strategies to treat malnutrition lack practicability in the hospital setting. The present study aimed at developing and evaluating a routinely manageable concept for an improved nutritional care of malnourished in-hospital patients.. A randomized controlled intervention study was conducted. 132 risk patients defined by Nutritional Risk Screening 2002, were randomized to individualised nutrition support (intervention group [n = 66]) or standard hospital care (control group [n = 66]). Body weight, plasma vitamin levels, quality of life, complications, antibiotic therapies, readmissions and mortality were assessed.. Nutrition interventions led to higher intakes (mean [standard deviation]) in energy (1553 [341] kcal vs. 1115 [381] kcal, p < 0.001) and protein (65.4 [16.4] g vs. 43.9 [17.2] g, p < 0.001). Intervention patients (n = 66) kept their body weight in comparison to control patients (n = 66; 0.0 [2.9] kg vs. -1.4 [3.2] kg, p = 0.008). Positive effects on plasma ascorbic acid level (46.7 [26.7] μmol/l vs. 34.1 [24.2] μmol/l, p = 0.010), SF-36 function summary scale (37 [11] % vs. 32 [9] %, p = 0.030), number of complications (4/66 vs. 13/66, p = 0.035), antibiotic therapies (1/66 vs. 8/66, p = 0.033) and readmissions (17/64 vs. 28/61, p = 0.027) were recorded.. Malnourished patients profit from nutrition support regarding nutrition status and quality of life. They have fewer complications, need fewer antibiotics and are less often re-hospitalised.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Aged, 80 and over; Analysis of Variance; Ascorbic Acid; Body Weight; Elder Nutritional Physiological Phenomena; Energy Intake; Female; Follow-Up Studies; Glutathione; Hospitalization; Humans; Male; Malnutrition; Mass Screening; Middle Aged; Nutritional Status; Quality of Life; Risk Factors; Surveys and Questionnaires; Treatment Outcome; Young Adult

Metabolism is probably disturbed in patients with abnormal liver function who have undergone a successful Kasai procedure. We examined bone mineral metabolism in patients who have successfully undergone Kasai procedure. Bone mineral metabolism was examined in 8 patients with biliary atresia after a successful Kasai procedure. Five patients were female and 3 were male. The ages at Kasai procedure ranged from 50 to 80 days, and the follow-up periods ranged from 3 to 27 years after the operation. All patients eat a normal oral diet. We examined plasma levels of 25-OH-D3, 1, 25-(OH)2-D3, Ca and phosphorus (P). Bone mineral content of the lumbar spine (L2-L4) was assessed by dual energy x-ray absorptiometry (DEXA), and the data were expressed as a bone mineral density (BMD). Two patients showed abnormal levels on hepatic function tests. Plasma levels of 1, 25-(OH)2-D3, Ca, and P were normal in all patients. The level of 25-OH-D3 was normal in 7 patients. BMD levels were normal in 6 patients, but low in 2 who had undergone partial splenic embolization and splenectomy, respectively, due to hypersplenism. In long-term survivors of Kasai procedure, measurement of BMD may detect bone mineral deficiency earlier than measurements of serum levels of 25-OH-D, 1, 25-(OH)2-D, Ca and P.

Topics: 24,25-Dihydroxyvitamin D 3; Absorptiometry, Photon; Adolescent; Adult; Biliary Atresia; Body Height; Body Weight; Bone Density; Calcium; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Liver Function Tests; Male; Portoenterostomy, Hepatic

Plasma 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentration was shown to decrease during bed rest in several studies when baseline plasma 25-hydroxyvitamin D (25-OHD) concentration was sub-optimal. Dahl salt-sensitive female (S) rats, but not Dahl salt-resistant female (R) rats, demonstrated a 50% decrease in plasma 1,25-dihydroxycholecalciferol (1,25-(OH)(2)D(3)) concentration after 28 days of hind limb unloading (HU, disuse model) during low salt intake (0.3%). We tested the vitamin D endocrine system response of female S rats to hind limb unloading during high salt intake (2%, twice that of standard rat chow to mimic salt intake in the USA). Hind limb unloading resulted in lower plasma 25-OHD(3) concentrations in S-HU rats than in R-HU rats (P<0.05) and greater urinary loss of 25-OHD(3) by S-HU rats than by S rats (P<0.05). Plasma 1,25-(OH)(2)D(3) concentration of S-HU rats was half that of S rats, but was unchanged in R-HU rats. The association of low plasma 25-OHD concentration with decrease in plasma 1,25-(OH)(2)D concentration of hind limb unloaded rats and of bed rest participants (published studies) suggests that low vitamin D status might be a risk factor for decrease in plasma vitamin D hormone concentration during long-term immobilization or bed rest.

Topics: 24,25-Dihydroxyvitamin D 3; Adrenal Glands; Animals; Blood; Body Weight; Calcifediol; Calcitriol; Calcium; Female; Hindlimb Suspension; Organ Size; Parathyroid Hormone; Protein Binding; Proteinuria; Rats; Rats, Inbred Dahl; Sodium; Sodium Chloride, Dietary

In patients with humoral hypercalcemia of malignancy (HHM), serum levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are generally low, although the pathophysiology of the impaired vitamin D metabolism is not fully understood. In the present study, we have investigated vitamin D metabolism in our newly developed rat model of HHM in which a human infantile fibrosarcoma producing parathyroid hormone-related protein (PTHrP), named OMC-1, was inoculated s.c. into athymic nude rats. In OMC-1-bearing rats, the serum concentration of 1,25(OH)(2)D was markedly reduced when the animals exhibited severe hypercalcemia (Ca > or =15 mg/dl), while it was rather elevated in those with mild hypercalcemia. To further examine whether serum Ca levels affect 1,25(OH)(2)D concentration, we administered bisphosphonate YM529 to OMC-1-bearing rats when they exhibited severe hypercalcemia. The restoration of the serum Ca level by administration of YM529 was accompanied by a marked increase in the 1,25(OH)(2)D level, suggesting that the serum Ca level itself plays an important role in the regulation of the 1,25(OH)(2)D level in these rats. On the other hand, when the OMC-1-bearing rats were treated with a neutralizing antibody against PTHrP, serum 1,25(OH)(2)D levels remained low despite the reduction in serum Ca levels. Expression of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) in kidney was decreased in OMC-1-bearing rats with severe hypercalcemia, and markedly enhanced after treatment with bisphosphonate. This enhancement in 1 alpha-hydroxylase expression was not observed after treatment with the antibody against PTHrP. These results suggest that PTHrP was responsible for the enhanced expression of 1 alpha-hydroxylase in YM529-treated rats, and that hypercalcemia played a role in reducing the serum 1,25(OH)(2)D level in OMC-1-bearing rats by suppressing the PTHrP-induced expression of the 1 alpha-hydroxylase gene.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Antibodies, Monoclonal; Blotting, Northern; Body Weight; Calcifediol; Calcitriol; Calcium; Calcium Channel Blockers; Diphosphonates; Fibrosarcoma; Gene Expression; Humans; Hypercalcemia; Imidazoles; Kidney; Male; Models, Animal; Neoplasm Transplantation; Parathyroid Hormone-Related Protein; Proteins; Rats; Rats, Nude; Reverse Transcriptase Polymerase Chain Reaction

In order to examine the influences by long-term feeding of 24R, 25 dihydroxyvitamin D3[24R, 25(OH)2D3], an active form of vitamin D, Wistar rats (14-week-old, male, 20 rats/group) were fed a powder diet containing 0 or 5 ppm 24R, 25(OH)2D3 for 57 weeks. Final body weights and total food consumption were comparable between the groups. Urinary calcium levels were significantly (p < 0.05 or 0.01) increased by the administration of 24R, 25(OH)2D3 at weeks 3, 22 and 56, although the levels of serum calcium did not differ between the groups at the termination of week 57. In the 24R, 25(OH)2D3 group, weights of the adrenals and femurs were significantly (p < 0.01) increased. Histopathologically, this was found due to thickening of cortical bone in the femurs, and medullary hyperplasia and pheochromocytoma of the adrenals. Immunohistochemically, proliferating cell nuclear antigen (PCNA)-labeling indices for intact adrenal medulla, medullary hyperplasia and pheochromocytoma in the 24R, 25(OH)2D3 group were respectively 1.82 +/- 1.21, 5.88 +/- 4.13 and 16, all higher than that for the adrenal medulla in the control group (0.87 +/- 0.67). These results indicate that 24R, 25(OH)2D3 at a dose with which serum calcium is not chronically increased causes thickening of the cortex of the femur, and development of adrenal proliferative lesions, suggesting that rats may be too sensitive for results to be relevant to human risk assessment.

Topics: 24,25-Dihydroxyvitamin D 3; Adrenal Cortex; Adrenal Gland Neoplasms; Adrenal Glands; Adrenal Medulla; Animals; Appetite; Body Weight; Calcium; Femur; Hyperplasia; Male; Organ Size; Pheochromocytoma; Phosphorus; Rats; Rats, Wistar

Serum levels of the vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D, and of osteocalcin, C-terminal parathyroid hormone and other biochemical indices related to bone metabolism, were determined in two groups of patients with beta-thalassaemia aged 5-10 years (summer 7.8 +/- 0.4 years, mean +/- SEM, and winter 7.7 +/- 0.4 years, group A, n = 15) and 11-23 years (16.6 +/- 0.9 and 15.7 +/- 0.9 years in summer and winter, respectively, group B, n = 22). Emphasis was given to populations of school and adolescent ages and to the seasons of summer and winter when vitamin D status demonstrates the widest extremes. The mean serum levels of 25-hydroxyvitamin D in patients aged 5-10 years did not differ from those of controls during both seasons studied. In contrast, in the age group 11-23 years these levels were found to be lower in patients than in controls both in winter (10.6 +/- 0.9 ng/ml vs 15.0 +/- 2.0 ng/ml, p < 0.05) and summer (20.2 +/- 2.1 ng/ml vs 27.1 +/- 2.0 ng/ml, p < 0.05). The serum concentrations of 24,25-dihydroxyvitamin D were lower in the thalassaemic patients than in controls in both age groups and both seasons. In the patients under 10 years of age the mean values of this metabolite in winter were 1.06 +/- 0.17 ng/ml vs 1.68 +/- 0.20 ng/ml in the respective controls (p < 0.05), and in summer 1.44 +/- 0.11 ng/ml vs 2.35 +/- 0.36 ng/ml in controls (p < 0.05). In the group of patients aged 11-23 years, the mean levels of 24,25-dihydroxyvitamin D were in winter 0.65 +/- 0.12 ng/ml vs 1.12 +/- 0.19 ng/ml (p < 0.05) in controls and in summer 1.34 +/- 0.12 ng/ml vs 1.84 +/- 0.20 ng/ml (p < 0.05). The 1,25-dihydroxyvitamin D concentrations in both thalassaemic patient groups were significantly no different from those in the respective control groups. Serum osteocalcin, C-terminal parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase levels in the patients studied were not significantly different from those in controls, except for calcium and phosphate in the older group. In the older group of thalassaemic patients, serum calcium was lower than in the controls (2.26 +/- 0.03 vs 2.37 +/- 0.03 mmol/l, p < 0.05) in summer and serum phosphate higher than in the controls in winter (1.47 +/- 0.05 mmol/l vs 1.27 +/- 0.06 mmol/l, p < 0.05).

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Adult; Age Factors; beta-Thalassemia; Body Weight; Child; Child, Preschool; Humans; Hydroxylation; Osteocalcin; Seasons; Vitamin D

It has recently been reported that new vitamin D3 derivatives can exert inhibitory effects on colon carcinogenesis in rats. In the present study the chemopreventive potential of 24R,25-dihydroxyvitamin D3 (24R,25(OH)2vitamin D3) was assessed in a murine model of colon carcinogenesis. In experiment 1, male 6-week-old F344 rats were administered N,N'-dimethylhydrazine (DMH) 20 mg/kg s.c. once a week 4 times. The rats were fed 24R,25(OH)2vitamin D3 at 10 ppm in the diet prior to (pre), together with (simultaneous) or after (post) DMH treatment. Modifying effects were assessed using aberrant crypt foci (ACF), putative preneoplastic lesions, as the end point markers in this model of colon carcinogenesis. After 8 weeks, pre and more markedly simultaneous administration of 24R,25(OH)2vitamin D3 was found to have reduced the total numbers of ACF and significantly inhibited the development of foci. After 16 weeks, numbers of foci with > or = 4 crypts, which are more likely to progress to tumors, were significantly reduced. The most pronounced inhibition of ACF development was noted in rats fed the 24R,25(OH)2vitamin D3 after DMH administration. The reduction was particularly marked in the proximal colon. Blood levels of calcium were not significantly increased over the control levels in groups administered DMH and the vitamin. Immunohistochemical staining showed numbers of proliferating cell nuclear antigen-positive cells to be lower in the colonic epithelia of rats fed the vitamin D3 metabolite than in the controls. In experiment 2, the effect of 24R,25(OH)2vitamin D3 on the alterations in c-fos, c-myc and c-jun oncogene expression in response to DMH administration was examined by northern blot analysis. The early increase in expression of ornithine decarboxylase (ODC) activity was not altered by 24R,25(OH)2vitamin D3. The results suggest that 24R,25(OH)2vitamin D3 is a cancer chemopreventive agent which may suppresses DMH induction of lesions and their subsequent development via an antiproliferative action.

Topics: 1,2-Dimethylhydrazine; 24,25-Dihydroxyvitamin D 3; Animals; Anticarcinogenic Agents; Body Weight; Calcium; Carcinogens; Cell Division; Colon; Colonic Neoplasms; Eating; Electrolytes; Epithelium; Male; Ornithine Decarboxylase; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Proto-Oncogenes; Rats; Rats, Inbred F344; RNA, Messenger; Time Factors

The effects of physiological concentrations of 1,25(OH)2D3 and 24,25(OH)2D3 on the intestinal Ca2+ uptake in the Atlantic cod (Gadus morhua) were investigated. The intestine was perfused, in vitro, both vascularly and through the intestinal lumen, and the Ca2+ influx was measured using 45Ca. At 2.02, 4.04, 10.1, and 20.2 nM 24,25(OH)2D3 decreased the Ca2+ influx across the intestinal mucosa by 21, 31, 34, and 28%, respectively, whereas perfusion with 1,25(OH)2D3 (concentrations: 85.3, 128, 256, and 640 pM) had no effect. The actions of 24,25(OH)2D3 were dose-related, observed within 10 to 25 min, and are concluded to affect intestinal Ca2+ influx via a rapid nongenomic mechanisms; 1,25(OH)2D3 seems to be without transcaltachic effect. Thus, for the rapid, short-term regulation of intestinal calcium uptake in the Atlantic cod, 24,25(OH)2D3 is a more important vitamin D3 metabolite, in contrast to other vertebrates in which 1,25(OH)2D3 is of major importance.

Topics: 24,25-Dihydroxyvitamin D 3; Analysis of Variance; Animals; Body Weight; Calcium; Calcium Radioisotopes; Female; Fishes; In Vitro Techniques; Intestinal Mucosa; Intestines; Male; Perfusion

To gain an insight in the regulation of (24R)-hydroxycalcidiol, we studied the pharmacokinetics of orally administered (24R)-hydroxycalcidiol in 6 healthy subjects without calcium supplementation, in 4 healthy subjects with calcium supplementation and in 6 patients with primary hyperparathyroidism. Various quantities related to calcium and vitamin D metabolism were also monitored. In the healthy subjects without calcium supplementation, the basal (24R)-hydroxycalcidiol concentration (Cb) in serum was 2.4 +/- 0.8 nmol/l (mean +/- SD, n = 5), the terminal serum half-time (t 1/2) 7.2 +/- 1.4 days, the production rate 0.05 +/- 0.01 nmol/kg.day, and the production rate/[calcidiol] ratio (1.5 +/- 0.4 x 10(-3) l/kg.day). In the healthy subjects studied, the serum concentration vs time curves exhibited a second maximum after administration, possibly due to binding by intestinal cells or (partial) uptake by the lymph system. In the calcium-supplemented healthy subjects, the pharmacokinetic quantities were not significantly different while the area under the serum concentration-time curve and the estimated bioavailability were significantly decreased. Basal concentration (Cb), production rate and the production rate/[calcidiol] ratio were significantly lower in patients with primary hyperparathyroidism but t 1/2 was unchanged. Exogenous (24R)-hydroxycalcidiol had no clear effect on calcium and vitamin D metabolism. In conclusion, a) exogenous (24R)-hydroxycalcidiol has no clear effect on calcium and vitamin D metabolism, b) clearance and production rate of (24R)-hydroxycalcidiol are not affected by calcium supplementation, c) bioavailability is lower in the calcium-supplemented state, d) basal concentration (Cb) and production rate are significantly decreased in patients with hyperparathyroidism.

Topics: 24,25-Dihydroxyvitamin D 3; Administration, Oral; Adult; Biological Availability; Body Weight; Calcifediol; Calcium; Half-Life; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Male; Middle Aged; Vitamin D

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Appetite; Atrophy; Body Weight; Bone and Bones; Calcitriol; Dogs; Female; Kidney; Kidney Diseases; Parathyroid Glands

Forty Fischer-344 rats (10 weeks old, 130 g BW) were either bilaterally ovariectomized (OVX) or sham-operated (SHAM). The rats were allocated to the following groups: SHAM; OVX; OVX + 15 ng 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]/rat/d; OVX + 30 ng 1 alpha,24R,25-trihydroxyvitamin D3 [1,24,25(OH)3D3]/rat/d; OVX + 15 ng 1,25(OH)2D3/rat/d + 30 ng 1,24,25(OH)3D3/rat/d. The vitamin D metabolites were fed orally starting 4 weeks after surgery. Urine and blood samples were taken at several time points during the experiment. Twenty-one weeks after surgery all rats were sacrificed, and the proximal tibiae and the first lumbar vertebrae were processed undecalcified for static bone histomorphometry. Ovariectomy induced a 40% reduction in vertebral cancellous bone area, and a 69% reduction in tibial cancellous bone area. This bone loss in OVX rats was associated with moderately increased biochemical and histomorphometric indices of bone formation and resorption as compared to values in sham-operated animals. Through inhibition of bone resorption, treatment of OVX rats with 1,25(OH)2D3, 1,24,25(OH)3D3, and the metabolite combination prevented the ovariectomy-induced osteopenia in the lumbar vertebra, and partially prevented cancellous bone osteopenia in the tibial metaphysis. However, OVX rats receiving 1,25(OH)2D3 alone or in combination with 1,24,25(OH)3D3 exhibited hypercalcemia, hyperphosphatemia, hypercalciuria, and impaired bone mineralization. Treatment of OVX rats with 1,24,25(OH)3D3 alone, on the other hand, only slightly increased serum calcium levels and did not impair bone mineralization. Furthermore, the inclusion of 1,24,25(OH)3D3 with 1,25(OH)2D3 partially antagonized the untoward effects of 1,25(OH)2D3 on bone mineralization. These data suggest that the actions of 1,24,25(OH)3D3 on bone metabolism might differ from that of 1,25(OH)2D3, and that 1,25(OH)2D3 and, particularly, 1,24,25(OH)3D3 may be potentially effective agents for the prophylaxis of postmenopausal osteoporosis.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Body Weight; Bone Diseases, Metabolic; Bone Resorption; Calcitriol; Female; Hydroxycholecalciferols; Lumbar Vertebrae; Ovariectomy; Rats; Rats, Inbred F344; Tibia

This study was conducted to determine the effect of feeding vitamin D3(D3) metabolites on BW of hen, weight of uterus, plasma Ca, jejunal and uterine adenosine triphosphatase (ATPase), and carbonic anhydrase. At 416 days of age each of 7 groups of laying hens was fed the basal ration supplemented with one of 7 concentrations (micrograms per kg) of D3 or its metabolites as treatments: 0 micrograms of D3; 27.5 micrograms of D3; 3, 5, or 7 micrograms of 1,25(OH)2D3; 5 micrograms of 24,25(OH)2D3; and 5 micrograms of 24,25(OH)2D3 plus 5 micrograms of 1,25(OH)2D3. Treatment effects were compared at various periods after the start of the study. Hens fed the unsupplemented ration had lower (P less than .05) values for all traits than hens fed the D3-supplemented ration by 162 days after the start of treatment. In a comparison of all dietary treatments except the one involving 0 micrograms D3, from 154 to 161 days after the start of the experiment, treatment effects were significant (P less than or equal to .05) for BW, uterine ATPase, and carbonic anhydrase; hens fed 5 micrograms of 24,25(OH)2D3 per kg of ration ranked the lowest of all treatment groups for these traits. Hens fed 27.5 micrograms of D3 and those fed 5 micrograms of 1,25(OH)2D3 per kg of ration did not differ (P greater than .05) for any traits studied. The results suggest that 5 micrograms of 1,25(OH)2D3 per kg of ration can replace 27.5 micrograms of D3 per kg of ration but that 5 micrograms of 24,25(OH)2D3 per kg of ration tends to have a negative effect on physiological systems of the hen.

Topics: 24,25-Dihydroxyvitamin D 3; Adenosine Triphosphatases; Animals; Body Weight; Calcitriol; Calcium; Carbonic Anhydrases; Chickens; Cholecalciferol; Female; Jejunum; Organ Size; Random Allocation; Uterus

In previous studies on calcium homeostasis in diabetes, drug-induced diabetic rats have generally been used, and various alterations have been demonstrated in several parameters of the vitamin D-endocrine system. It is, however, still questionable whether the drug-induced diabetic rat is the most appropriate animal model for the investigation of calcium and vitamin D metabolism because of the toxicity of diabetogenic agents toward the principle organs of vitamin D metabolism, such as liver and kidney. Therefore, in the present study, we examined the strain of genetically diabetic mice, C57BL/KsJ db/db, to evaluate 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors in intestine and kidney and to investigate the alterations of calcium and vitamin D metabolism. In both control and diabetic mice, intestinal and renal 1,25-(OH)2D3 receptors were demonstrated; they had a sedimentation coefficient of 3.4S. The number of specific 1,25-(OH)2D3-binding sites in intestine was 118 +/- 11 fmol/mg protein in diabetic mice, significantly lower than the value of 199 +/- 11 fmol/mg protein in controls (P less than 0.01). Moreover, the renal concentration of specific 1,25-(OH)2D3-binding sites of 34.6 +/- 7.1 fmol/mg protein in diabetic mice was also significantly reduced compared to the value of 63.3 +/- 5.7 fmol/mg protein in controls (P less than 0.01). There were no significant differences in the equilibrium dissociation constants (Kd) of intestinal and renal receptors between control and diabetic mice. Significant hypocalcemia was demonstrated in the diabetic mice (P less than 0.01), suggesting the development of a negative calcium balance. Diabetic mice showed a significant decrease in renal 24,25-(OH)2D3 production (P less than 0.02), whereas renal 1,25-(OH)2D3 production was significantly increased in the diabetic group (P less than 0.05) compared to the control value. It is probable from these results that the genetic/endogenous diabetes may be directly associated with the alterations of mineral homeostasis. The altered calcium and vitamin D metabolism in diabetic mice is suggested to be derived, at least in part, from the decreased number of the 1,25-(OH)2D3 receptors in both intestine and kidney in the diabetic state.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Blood Glucose; Body Weight; Calcifediol; Calcitriol; Calcium; Diabetes Mellitus, Experimental; Dihydroxycholecalciferols; Insulin; Intestinal Mucosa; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Receptors, Calcitriol; Receptors, Steroid

It has previously been shown that vitamin D deficiency impairs arginine-induced insulin secretion from the isolated, perfused rat pancreas (Science 1980; 209:823-25). Since vitamin D is known to be metabolized to 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) and 24R,25-dihydroxyvitamin D3 (24,25[OH]2D3), it is essential to clarify which vitamin D metabolite has the important role of enhancing insulin secretion. In this report, a comparison is made of the relative efficacy of 3-wk repletion with vitamin D3 (980 pmol/day), 1,25(OH)2D3 (39 pmol/day or 195 pmol/day), and 24,25(OH)2D3 (650 pmol/day) on arginine-induced insulin secretion from the isolated, perfused rat pancreas; in this experiment, the daily caloric intake of the animals receiving vitamin D or its metabolites was controlled by pair feeding to the caloric intake of the vitamin D-deficient rats. 1,25(OH)2D3 repletion was found to completely restore insulin secretion to the levels seen in vitamin D3-replete, pair-fed controls in both the first and second phases, while 24R,25(OH)2D3 only partially improved insulin secretion, and then only in the first phase. Changes of both serum calcium levels and dietary caloric intake after vitamin D metabolite administration are concluded to play a lesser role on the enhancement of insulin secretion, since, in a separate experiment, vitamin D-deficient rats with normal serum calcium levels did not show recovery of insulin secretion equivalent to the vitamin D-replete animals under conditions of dietary pair feeding. These results suggest that 1,25(OH)2D3 but not 24,25(OH)2D3 plays an essential role in the normal insulin secretion irrespective of the dietary caloric intake and prevailing serum calcium levels.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Arginine; Body Weight; Calcitriol; Calcium; Cholecalciferol; Dihydroxycholecalciferols; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Male; Perfusion; Rats; Vitamin D Deficiency

In order to investigate mineral and vitamin D metabolism in obese rats with hyperinsulinemia, plasma calcium and vitamin D metabolites were measured in Zucker fa/fa rats. Body weight, plasma insulin, and calcium in fa/fa rats were significantly increased compared to their lean littermates (p less than 0.01). However, no significant difference in plasma 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) or the ratio of 1,25(OH)2D to 25(OH)D was observed between fa/fa rats and their lean littermates. The hypercalcemia in the rats with hyperinsulinemia, therefore, might be caused by other calcium-regulating hormones or some factors other than 1,25(OH)2D. In addition, the hyperinsulinemia associated with obesity may not produce the accelerated conversion from 25(OH)D into 1,25(OH)2D.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Blood Glucose; Body Weight; Calcifediol; Calcitriol; Dihydroxycholecalciferols; Hypercalcemia; Hyperinsulinism; Male; Obesity; Rats; Rats, Zucker; Vitamin D

This study examined the influence of 24,25 (OH)2D3, an active metabolite of vitamin D, on the growth and development of cartilage cells in condylar cartilage of suckling mice. It became evident that when the hormone was administered even at high doses, it did not significantly affect the incorporation of [3H]thymidine, but led to a marked decrease in the number of both chondroblasts and hypertrophic chondrocytes. At the same time, condyle of hormone-treated mice reached an increase in the number of mesenchymelike cells within the chondroprogenitor zone. High values of correlation were noted between the overall dimensions of the condylar cartilage and those of the chondroblastic and hypertrophic zones. The hormone also significantly reduced the degree of matrix metachromasia (indicative of proteoglycan content) and concomitantly altered the mineralization pattern of the cartilaginous matrix. This study indicates that in young animals increased doses of 24,25(OH)2D3 do not affect the proliferative activity of chondroprogenitor cells yet possess an inhibitory effect upon the capacity of the latter cells to differentiate into chondroblasts. The hormone also seems to affect the already differentiated cells--chondroblasts and hypertrophic chondrocytes--both structurally as well as metabolically. In so doing, this metabolite of vitamin D affects the normal process of endochondral bone formation in one of the mandible's main growth sites. Thus, in the developing animal, elevated concentrations of 24,25(OH)2D3 may impair the growing mandible's ability to achieve its normal size and shape.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Animals, Suckling; Body Weight; Cartilage; Dihydroxycholecalciferols; Female; Male; Mandibular Condyle; Mice; Mice, Inbred ICR; Proteoglycans; Thymidine

Bone formation, mineralization, and resorption were measured in vitamin D-deficient, azotemic rats given two different dosages of 24,25(OH)2D3 daily and in vehicle-treated controls (C). The intraperitoneal administration of 65 pmol over a 10 day period corrected the hypocalcemia observed in C, whereas 130 pmol produced mild hypercalcemia. Both dosages reduced osteoid width, osteoid area, and mineralization front width from control values. The rates of bone and matrix formation were unaffected by treatment. In C, matrix formation exceeded bone formation and resulted in osteoid accumulation; both dosages of 24,25(OH)2D3 reversed this relationship such that bone formation exceeded matrix formation in each treatment group. The rates of osteoid maturation and initial mineralization increased during repletion with 24,25(OH)2D3 at both dosage levels. However, the serum calcium concentration was correlated with both osteoid maturation rate (r = 0.68, P less than 0.01) and initial mineralization rate (r = 0.63, P less than 0.01) when all three experimental groups were considered. Bone resorption was unchanged from control values during treatment with 24,25(OH)2D3. The results suggest that 24,25(OH)2D3 promotes the maturation and mineralization of osteoid, and that this metabolite differs in its effects on bone formation and resorption. It is not clear, however, that the changes in bone dynamics observed are independent of the calcemic response induced by metabolite repletion under the conditions of this experiment.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Blood Urea Nitrogen; Body Weight; Bone and Bones; Bone Development; Bone Matrix; Bone Resorption; Calcium; Dihydroxycholecalciferols; Injections, Intraperitoneal; Male; Osteogenesis; Phosphorus; Rats; Vitamin D Deficiency

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Body Weight; Calcitriol; Creatinine; Cyclic AMP; Diabetes Mellitus, Experimental; Dihydroxycholecalciferols; Insulin; Kidney; Male; Parathyroid Hormone; Rats; Rats, Inbred F344

One-day-old chicks were depleted of vitamin D. At 3 weeks their right tibiae, and those of a control group given vitamin D3, were fractured and pinned. After fracture the controls were kept on vitamin D3. Another group was left vitamin D-deficient. The remaining depleted chicks, divided into four groups, were given vitamin D3, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or a combination of 24,25(OH)2D3 and 1,25(OH)2D3. The callus obtained after 9 and 14 days was subjected to torsional stress. The callus of chicks given vitamin D continuously showed the greatest resistance, whereas that of vitamin D-deficient chicks showed the smallest resistance. Repletion with either vitamin D3 or its metabolites increased the strength of the callus. Repletion with the combination of 24,25(OH)2D3 and 1,25(OH)2D3 produced the most marked results, in that the callus was even stronger than that of chicks replete with vitamin D3. It is concluded that 24,25(OH)2D3 is essential for bone formation in addition to the known active vitamin D metabolite 1,25(OH)2D3, and the possible clinical implications of these findings are discussed.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Body Weight; Bony Callus; Calcitriol; Calcium; Chickens; Cholecalciferol; Dihydroxycholecalciferols; Male; Phosphates; Stress, Mechanical; Tibial Fractures; Wound Healing

In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-dihydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Animals; Blood Glucose; Blood Urea Nitrogen; Body Weight; Calcifediol; Calcitriol; Calcium; Chromatography, High Pressure Liquid; Creatinine; Diabetes Mellitus, Experimental; Dihydroxycholecalciferols; Ergocalciferols; Hydroxycholecalciferols; Insulin; Kidney Function Tests; Liver Function Tests; Male; Rats; Rats, Inbred Strains

Hypophysectomy of animals given maintenance levels of vitamin D and adequate levels of dietary calcium and phosphorus brings about a marked reduction in plasma 1,25-dihydroxyvitamin D3 levels and a significant elevation in plasma 24,25-dihydroxyvitamin D3 levels. The hypophysectomy, as expected, results in reduced growth and lowered plasma levels of inorganic phosphorus. The injection of growth hormone markedly increases plasma levels of 1,25-dihydroxyvitamin D3 in hypophysectomized animals while bringing about a reduction in 24,25-dihydroxyvitamin D3 levels. These results support the idea that the hypophysis plays a role in the regulation of vitamin D metabolism and that growth hormone either directly or indirectly is one of the hypophyseal factors bringing about this regulation.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Body Weight; Calcitriol; Calcium; Dihydroxycholecalciferols; Growth Hormone; Hypophysectomy; Male; Organ Size; Phosphorus; Pituitary Gland; Rats; Vitamin D