scholarly journals Human duodenum responses to vitamin D metabolites of TRPV6 and other genes involved in calcium absorption

2009 ◽  
Vol 297 (6) ◽  
pp. G1193-G1197 ◽  
Author(s):  
Sara Balesaria ◽  
Sonia Sangha ◽  
Julian R. F. Walters
Keyword(s):  
Vitamin D ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Calcium Absorption ◽  
Bone Mineralization ◽  
Duodenal Mucosa ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Normal Human ◽  
Major Factors

Calcium absorption by the intestine is necessary for bone mineralization. Much has been learned about this process and the role of vitamin D metabolites in gene transcription from animal studies, but the molecular mechanisms in humans are less well understood. We have used samples of normal human duodenal mucosa, obtained at endoscopy, to investigate the effects of the vitamin D metabolites, 1α-dihydroxycholecalciferol [1,25(OH)2D3] and 25-hydroxycholecalciferol (25OHD), on transcripts on genes involved in calcium absorption and vitamin D metabolism. TRPV6 transcripts were significantly higher after incubation for 6 h with 1,25(OH)2D3 (10−9 mol/l) than after control incubations (median difference 3.1-fold, P < 0.001). Unexpectedly, TRPV6 expression was also higher (2.4-fold, P < 0.02) after incubation with 25OHD (10−7 mol/l). Transcripts for the calcium-ATPase, PMCA1, were significantly higher with 1,25(OH)2D3; CYP24 transcripts were reliably detected after incubation with either metabolite, but calbindin-D9k transcripts were unaffected. The response of TRPV6 to 25OHD and the expression of transcripts for CYP27B1, the 25OHD-1α-hydroxylase, were significantly correlated ( r = 0.82, P < 0.02). Basal duodenal expression of TRPV6 and CYP27B1 were significantly associated ( r = 0.72, P < 0.001) in a separate previously reported series of subjects. Multiple regression analysis of the associations with basal duodenal TRPV6 expression identified CYP27B1 expression and serum 1,25(OH)2D as major factors. Expression of the CYP27B1 protein was demonstrated immunohistochemically in duodenal mucosa. This study has shown that human duodenal TRPV6, PMCA1, and CYP24 transcripts respond rapidly to 1,25(OH)2D3 and provides evidence suggesting that local duodenal production of 1,25(OH)2D3 by 25OHD-1α-hydroxylase may have a role in human calcium absorption.

scholarly journals Parathyroid hormone-independent hypercalcemia and hypercalciuria of a patient with nephrolithiasis and nephrocalcinosis and impaired vitamin D metabolism due to a defect in the CYP24A1 gene

2021 ◽  
Vol 24 (1) ◽  
pp. 26-33
Author(s):  
L. Ya. Rozhinskaya ◽  
A. S. Pushkareva ◽  
E. O. Mamedova ◽  
V. P. Bogdanov ◽  
V. V. Zakharova ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Calcium Absorption ◽  
Genetic Research ◽  
Autosomal Recessive Disorder ◽  
Malignant Neoplasms ◽  
Vitamin D Metabolites ◽  
Active Metabolites ◽  
Vitamin D Metabolism ◽  
Severe Hypercalcemia

Hypercalcemia associated with impaired vitamin D metabolism is a rare autosomal recessive disorder. The mechanism of this pathology is the impairment of inactivation of active metabolites of vitamin D because of mutations in the CYP24A1 gene, which leads to an increase of calcium absorption and the development of hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. The phenotype of the disease ranges from severe forms which are diagnosed in early infancy (severe hypercalcemia associated with dehydration, vomiting, nephrocalcinosis, and sometimes death) to milder forms, that often are diagnosed in adulthood and manifested with recurrent nephrolithiasis and nephrocalcinosis. Differential diagnosis is carried out with the most common causes of hypercalcemia: primary hyperparathyroidism and malignant neoplasms. To diagnose, the determination of vitamin D metabolites and genetic research are used. As a treatment for mild forms, it is recommended to limit dairy products, to keep a drinking regimen, to refuse taking vitamin D and calcium preparations, and use of sunscreens. The article presents a clinical case of parathyroid hormone-independent hypercalcemia due to mutation of the CYP24A1 gene of a 20-year-old patient suffering from nephrolithiasis and nephrocalcinosis since the age of 16 with a confirmed violation of vitamin D metabolism.

scholarly journals Implications of Vitamin D Research in Chickens can Advance Human Nutrition and Perspectives for the Future

2021 ◽  
Author(s):  
Matthew F Warren ◽  
Kimberly A Livingston
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D Supplementation ◽  
The Body ◽  
Human Nutrition ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Related Research ◽  
Vitamin D Intake ◽  
Increased Risk

Abstract The risk of vitamin D insufficiency in humans is a global problem that requires improving ways to increase vitamin D intake. Supplements are a primary means for increasing vitamin D intake, but without a clear consensus on what constitutes vitamin D sufficiency, there is toxicity risk with taking supplements. Chickens have been used in many vitamin D-related research studies, especially studies involving vitamin D supplementation. Our state-of-the-art review evaluates vitamin D metabolism and how the different hydroxylated forms are synthesized. We provide an overview with how vitamin D is absorbed, transported, excreted, and what tissues in the body store vitamin D metabolites. We also discuss a number of studies involving vitamin D supplementation with broilers and laying hens. Vitamin D deficiency and toxicity are also described and how they can be caused. The vitamin D receptor (VDR) is important for vitamin D metabolism. However, there is much more that can be understood with VDR in chickens. Potential research aims involving vitamin D and chickens should explore VDR mechanisms which could lead to newer insights with VDR. Utilizing chickens in future research to help with elucidating vitamin D mechanisms has great potential to advance human nutrition. Finding ways to increase vitamin D intake will be necessary because the coronavirus 2019 disease (COVID-19) pandemic is leading to increased risk of vitamin D deficiency in many populations. Chickens can provide a dual purpose with addressing pandemic-caused vitamin D deficiency: 1) vitamin D supplementation gives chickens added value with possibly leading to vitamin D-enriched meat and egg products; and 2) chickens’ use in research provides data for translational research. Expanding vitamin D-related research in chickens to include more nutritional aims in vitamin D status has great implications with developing better strategies to improve human health.

scholarly journals Evaluation of Vitamin D Metabolism in Patients with Type 1 Diabetes Mellitus in the Setting of Cholecalciferol Treatment

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3873
Author(s):  
Alexandra Povaliaeva ◽  
Ekaterina Pigarova ◽  
Artem Zhukov ◽  
Viktor Bogdanov ◽  
Larisa Dzeranova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Controlled Study ◽  
Affinity Constant ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels

In this prospective controlled study, we examined 25 adults with adequately controlled (HbA1c level < 8.0%) type 1 diabetes mellitus (T1DM) and 49 conditionally healthy adults, intending to reveal the diversity of vitamin D metabolism in the setting of cholecalciferol intake at a therapeutic dose. All patients received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. The studied groups had no significant differences in baseline parameters except that the patients with diabetes showed higher baseline levels of free 25(OH)D (p < 0.05). They also lacked a correlation between the measured and calculated free 25(OH)D in contrast to the patients from the control group (r = 0.41, p > 0.05 vs. r = 0.88, p < 0.05), possibly due to the glycosylation of binding proteins, which affects the affinity constant for 25(OH)D. The elevation of vitamin D levels after the administration of cholecalciferol was comparable in both groups, with slightly higher 25(OH)D3 levels observed in the diabetes group throughout the study since Day 1 (p < 0.05). Overall, our data indicate that in patients with adequately controlled T1DM 25(OH)D3 levels and the therapeutic response to cholecalciferol is similar to that in healthy individuals.

scholarly journals Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4329
Author(s):  
Alexandra Povaliaeva ◽  
Viktor Bogdanov ◽  
Ekaterina Pigarova ◽  
Artem Zhukov ◽  
Larisa Dzeranova ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cushing’S Disease ◽  
Serum Vitamin ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Control Group ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Serum Vitamin D ◽  
Free Cortisol

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently lower 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

THE SMALL INTESTINE IN VITAMIN D DEPENDENT RICKETS

PEDIATRICS ◽  
1970 ◽  
Vol 45 (3) ◽  
pp. 364-373
Author(s):  
Richard Hamilton ◽  
Joan Harrison ◽  
Donald Fraser ◽  
Lngeborg Radde ◽  
Rachel Morecki ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Vitamin D ◽  
Calcium Absorption ◽  
Light And Electron Microscopy ◽  
Intestinal Transport ◽  
Duodenal Mucosa ◽  
Intestinal Function ◽  
Active Vitamin ◽  
Phosphorus Absorption ◽  
Deficiency Rickets

We have demonstrated impaired intestinal absorption of calcium in a child with active vitamin D dependent rickets (hereditary pseudovitamin D deficiency rickets) at a time when the patient had normal anti-rachitic activity in her serum. Calcium absorption improved greatly in response to vitamin D, administered in the massive dosage that was necessary to heal the rachitic lesions. Phosphorus absorption may have been slightly impaired in the same patient, but no other absorptive defect was found. We studied intestinal function in five additional patients after they had been placed on vitamin D therapy. No abnormalities were found. In these treated patients, calcium absorption was not measured. Duodenal mucosa studied by light and electron microscopy was normal in all patients. Future investigation of intestinal transport of calcium in these patients should help to explain the pathogenesis of this disease.

scholarly journals Vitamin D Metabolism and Profiling in Veterinary Species

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 371 ◽  
Author(s):  
Emma A. Hurst ◽  
Natalie Z. Homer ◽  
Richard J. Mellanby
Keyword(s):  
Vitamin D ◽  
Companion Animals ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Health And Disease ◽  
25 Hydroxyvitamin D

The demand for vitamin D analysis in veterinary species is increasing with the growing knowledge of the extra-skeletal role vitamin D plays in health and disease. The circulating 25-hydroxyvitamin-D (25(OH)D) metabolite is used to assess vitamin D status, and the benefits of analysing other metabolites in the complex vitamin D pathway are being discovered in humans. Profiling of the vitamin D pathway by liquid chromatography tandem mass spectrometry (LC-MS/MS) facilitates simultaneous analysis of multiple metabolites in a single sample and over wide dynamic ranges, and this method is now considered the gold-standard for quantifying vitamin D metabolites. However, very few studies report using LC-MS/MS for the analysis of vitamin D metabolites in veterinary species. Given the complexity of the vitamin D pathway and the similarities in the roles of vitamin D in health and disease between humans and companion animals, there is a clear need to establish a comprehensive, reliable method for veterinary analysis that is comparable to that used in human clinical practice. In this review, we highlight the differences in vitamin D metabolism between veterinary species and the benefits of measuring vitamin D metabolites beyond 25(OH)D. Finally, we discuss the analytical challenges in profiling vitamin D in veterinary species with a focus on LC-MS/MS methods.

scholarly journals Intestinal Calcium Absorption and Serum Vitamin D Metabolites in Normal Subjects and Osteoporotic Patients

1979 ◽  
Vol 64 (3) ◽  
pp. 729-736 ◽  
Author(s):  
J. C. Gallagher ◽  
B. Lawrence Riggs ◽  
John Eisman ◽  
Alan Hamstra ◽  
Sara B. Arnaud ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Absorption ◽  
Serum Vitamin ◽  
Normal Subjects ◽  
Intestinal Calcium Absorption ◽  
Vitamin D Metabolites ◽  
Serum Vitamin D

Epithelial calcium transporter expression in human duodenum

2001 ◽  
Vol 280 (2) ◽  
pp. G285-G290 ◽  
Author(s):  
Natalie F. Barley ◽  
Alison Howard ◽  
David O'Callaghan ◽  
Stephen Legon ◽  
Julian R. F. Walters
Keyword(s):  
Vitamin D ◽  
Calcium Channel ◽  
Calcium Absorption ◽  
Apical Membrane ◽  
Calcium Influx ◽  
Basolateral Membrane ◽  
Cdna Probe ◽  
Vitamin D Metabolites ◽  
Expression Of Genes ◽  
Calbindin D

Calcium absorption in intestine and kidney involves transport through the apical membrane, cytoplasm, and basolateral membrane of the epithelial cells. Apical membrane calcium influx channels have recently been described in rabbit (epithelial calcium channel, ECaC) and rat (calcium transport protein, CaT1). We amplified from human duodenum a 446-base partial cDNA probe (ECAC2) having a predicted amino acid similarity of 97% to rat CaT1. Duodenum, but not ileum, colon, or kidney, expressed a 3-kb transcript. A larger transcript was also found in placenta and pancreas, and a different, faint transcript was found in brain. In duodenal biopsies from 20 normal volunteers, expression varied considerably but was not significantly correlated with vitamin D metabolites. This signal correlated with calbindin-D9k ( r = 0.48, P< 0.05) and more strongly with the plasma membrane calcium ATPase PMCA1 ( r = 0.83, P < 0.001). These data show that although individual variations in calcium channel transcripts are not vitamin D dependent, expression of genes governing apical entry and basolateral extrusion are tightly linked. This may account for some of the unexplained variability in calcium absorption.

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