The Metabolism, Physiology, and Function of Vitamin D

DeLuca, Hector F.

doi:10.1007/978-1-4613-2839-1_1

Cited by 35 publications

(25 citation statements)

References 275 publications

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“…Other studies showed that administration of lIa,25(OH)2D3 significantly prolonged the life of mice injected with the Ml transplantable leukemia cells (30). Our present study found, however, that the 50% effective concentration of la,25(OH)2D3 that is required both for clonal inhibition and differentiation of human leukemic cells in vitro is 10-100-fold higher than the serum level of la,25(OH)2D3 present in vivo (31). In addition, a smaller percentage of la,25(0H)2D3 is bound to binding proteins in our culture conditions than is bound in normal human plasma, which might preferentially increase the in vitro as compared with the in vivo potency of I a,25(OH)2D3.…”

Section: Discussioncontrasting

confidence: 81%

Vitamin D compounds. Effect on clonal proliferation and differentiation of human myeloid cells.

Munker¹,

Norman²,

Koeffler³

1986

J. Clin. Invest.

178

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We examined the effect of la,25-dihydroxyvitamin D3 (la,25(0H)2D3) and a variety of vitamin D analogs on proliferation and differentiation of normal and leukemic myeloid clonogenic cells. Only cells from myeloid leukemic lines that contained relatively mature cells (HL-60, U937, THP, HEL, Ml) were induced to differentiate and were inhibited in their clonal growth by exposure to la,25(0H)hD (50% inhibition, 3 X 10-8-8 X 10-1O M). A fluorinated analog of vitamin D was 5-10-fold more potent than la,25(OH)2D3. Cells from a human myeloblast line (KG-1) and normal human granulocyte-monocyte stem cells (GM-CFC), both of which depend on colony-stimulating factor (CSF) for clonal growth, were stimulated in their clonal proliferation by la,25(OH)2D3 in the presence of suboptimal concentrations of CSF. Leukemic cells from 10 of 14 patients with myeloid leukemia, but not normal GM-CFC from 12 patients in remission, were markedly inhibited in their clonal proliferation by la,25(0H)2D3. Our results suggest that la,25(OH)2D3 may be a cofactor in hematopoiesis and that vitamin D analogs may have a differential effect on normal versus leukemic growth.

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Section: Discussioncontrasting

confidence: 81%

Vitamin D compounds. Effect on clonal proliferation and differentiation of human myeloid cells.

Munker¹,

Norman²,

Koeffler³

1986

J. Clin. Invest.

178

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“…Indeed, tissue expression of VDR is directed by a number of promoters and transcription initiation from exons 1a or 1d, and alternative splicing can generate at least 10 different VDR transcripts, each of which was found in all of the tissues examined by Crofts et al (50). Furthermore, we have previously studied mouse fibroblast and intestinal cell lines and showed that the addition of calcitriol [1,25(OH) 2 D] increased VDR protein levels without changes in mRNA (51); similar changes have been reported in humans for healthy macrophages (49).…”

Section: Discussionmentioning

confidence: 88%

“…Furthermore, VDR expression has been shown to be a determinant of insulin secretory capacity. Diabetes 51:2294 -2312, 2002 C lassic actions of vitamin D include maintenance of mineral homeostasis by regulation of calcium absorption in the gut and reabsorption by the kidney, in addition to regulation of bone remodeling (1). Among many noncalcemic functions are the induction of differentiation in peripheral blood mononuclear cells (PBMCs) and antiproliferative effects in many cancers, as well as vitamin D's immunosuppressive properties; vitamin D also acts as a necessary adjunct for insulin secretion (2).…”

mentioning

confidence: 99%

“…The main sources of vitamin D are ergocalciferol (D2) and cholecalciferol (D3), found in dietary sources and supplements, and cholecalciferol produced in the skin by ultraviolet radiation of 7-dehydrocholesterol. Both these compounds are hydroxylated in the liver to form 25- (1,3). The 25(OH)D precursor is widely used in assessment of vitamin D repletion and has a slower rate of clearance from the circulation than 1,25(OH) 2 D. Because the VDR is expressed in a large number of tissues, it is not surprising that ligand-activated VDR modulates the expression of many genes.…”

mentioning

confidence: 99%

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Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

et al. 2002

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Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabetes, insulin secretion, and the insulin resistance syndrome. As VDR polymorphisms have no known functional significance, these findings may implicate a variant of the VDR gene or a locus in linkage disequilibrium with the VDR. We have examined VDR mRNA and VDR protein levels in relation to VDR polymorphisms (41 Bangladeshi subjects) and analyzed insulin secretory capacity (143 Bangladeshi subjects), allowing for other known determinants. Peripheral blood mononuclear cells (PBMCs) from subjects who had been genotyped for BsmI, ApaI, TaqI, and FokI VDR restriction fragment length polymorphisms were used for both total VDR mRNA quantitation (using TaqMan) and measurement of VDR protein levels (using a specific microimmunoassay). Stepwise multiple regression analyses were used (to P < 0.05) to analyze the data. For the insulin secretion index, the best-fit model (n ‫؍‬ 143, P < 0.0001) gave age (P ‫؍‬ 0.002), TaqI (P < 0.0001), and BMI (P ‫؍‬ 0.001) as independent determinants; with the inclusion of VDR mRNA and VDR protein levels, VDR mRNA was the sole independent determinant (n ‫؍‬ 41, P ‫؍‬ 0.024). However, the best-fit model for VDR mRNA (P ‫؍‬ 0.004) gave FokI (P ‫؍‬ 0.044) and TaqI (P ‫؍‬ 0.04) genotypes and insulin secretory capacity (P ‫؍‬ 0.042) as independent determinants. For VDR protein levels, the best-fit model (P ‫؍‬ 0.006) gave TaqI genotype (P ‫؍‬ 0.005) and circulating 1,25-dihydroxyvitamin-D levels (P ‫؍‬ 0.03) as independent determinants. In conclusion, these studies confirm an association between VDR polymorphisms and insulin secretory capacity and demonstrate the VDR genotype to be a significant determinant of VDR mRNA and VDR protein levels in PBMCs, providing functional support to previously described genetic associations with the VDR gene. Furthermore, VDR expression has been shown to be a determinant of insulin secretory capacity. Because the VDR is expressed in a large number of tissues, it is not surprising that ligand-activated VDR modulates the expression of many genes. The VDR gene, located on chromosome 12q, has 14 exons, 6 of which are in the 5Ј untranslated region (1a-1f). At least 22 unique nonfunctional VDR variants have been described, most of which lead to rare syndromes associated with vitamin D-resistant rickets (4). A number of common chronic disorders of inflammatory, infective, and autoimmune etiologies, including both type 1 and type 2 diabetes and colorectal adenoma, have been shown to be associated with specific polymorphisms of the vitamin D receptor gene, although not all such associ-

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“…However, although the OR for risk allele 'A' in the TNF-α gene was computed at 2.2, the low frequency of occurrence of this allele in both genotypic conditions (homozygous: 5% in T2D vs 0% in NGT and heterozygous: 7.5% in each T2D and NGT cases) indicated that the association was not significant. The primary role of vitamin D includes maintenance of mineral homeostasis by controlling calcium absorption in the gut and re-absorption by the kidney (DeLuca, 1984). However, although best known for their role in calcium uptake there are a host of other non-calcemic activities that vitamin D performs, primary among them being the induction of differentiation in peripheral blood mononuclear cells (PBMCs), and anti-proliferative effects in many forms of cancer.…”

Section: Resultsmentioning

confidence: 99%

Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in

Mukhopadhyaya¹,

Acharya²,

Chavan³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. A population-based study was undertaken to evaluate linkage between single-nucleotide polymorphisms known as risk factors and type 2 diabetes in an Indian population. The study population was comprised of 40 normal glucose-tolerant individuals (21 males and 19 females) and 40 type 2 diabetes patients (21 males and 19 females). The genes and their corresponding single-nucleotide polymorphisms that we screened were VDR (rs 731236 and rs 1544410), IL-6 (rs 1800795), TCF7L2 (rs 7903146) and TNF-α (rs 1800629). The risk alleles were more frequent in the subjects with type 2 diabetes, except for the TNF-α gene, which was very infrequent in the population; the normal allele occurred at high and similar frequencies in both normal and diabetic individuals.

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The Metabolism, Physiology, and Function of Vitamin D

Cited by 35 publications

References 275 publications

Vitamin D compounds. Effect on clonal proliferation and differentiation of human myeloid cells.

Vitamin D compounds. Effect on clonal proliferation and differentiation of human myeloid cells.

Vitamin D Receptor (VDR) mRNA and VDR Protein Levels in Relation to Vitamin D Status, Insulin Secretory Capacity, and VDR Genotype in Bangladeshi Asians

Metagenomic study of single-nucleotide polymorphism within candidate genes associated with type 2 diabetes in

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