Vitamin D is not linked to folate status and mRNA expression of intestinal proton-coupled folate transporter
Corinna BrandschJuliane ZibolkaMatthias FrommhagenUlrike LehmannJutta DierkesH KühneFrank HircheGabriele I. Stangl
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The liver plays an essential role in removing endogenous and exogenous compounds from the circulation. This function is mediated by specific transporters, including members of the family of organic anion transport proteins (OATPs) and the Na + ‐taurocholate transporting polypeptide (NTCP). In the present study, transporter protein expression was determined in liver samples from patients with cirrhosis or controls without liver disease. Five transporters (OATP1A2, OATP1B1, OATP1B3, OATP2B1, and NTCP) were studied. Transporter content in homogenates of human liver was quantified on western blots probed with transporter‐specific antibodies in which a calibrated green fluorescent protein‐tagged transporter standard was included. Liver samples from 21 patients with cirrhosis (hepatitis C in 17 and alcohol abuse in 4) and 17 controls without liver disease were analyzed. Expression of each of the transporters had a large spread, varying by an order of magnitude in cirrhotic and control livers. OATP1B1 was the most abundant transporter in controls ( P < 0.01) but was significantly lower in cirrhotic livers as was NTCP expression ( P < 0.01). There was little difference in transporter expression with respect to age or sex. Despite the large variability in transporter expression within a group, analysis in individuals showed that those with high or low expression of one transporter had a similar magnitude in expression of the others. Conclusion: Differences in transporter expression could explain unanticipated heterogeneity of drug transport and metabolism in individuals with and without liver disease.
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Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status.Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3.This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18-84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter.Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean+/-sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9+/-10.5 ng/ml; 11 wk 26.8+/-9.6 ng/ml), vitamin D3 (baseline 19.6+/-11.1 ng/ml; 11 wk 28.9+/-11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2+/-10.4 ng/ml; 11 wk 28.4+/-7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml.A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.
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Vitamin D and its metabolites are crucial to the overall health and well-being of humans and animals, having important functions in calcium homeostasis and bone metabolism. Exposure of the skin to sunlight may provide adequate levels of vitamin D; however, there are numerous reports of vitamin D insufficiency or deficiency. 25-hydroxyvitamin D (calcidiol, 25(OH)D) is regarded as the best measurement of overall vitamin D status. 1,25-dihydroxyvitamin D (calcitriol, 1,25(OH)2D) is the most biologically active vitamin D metabolite. 25(OH)D has higher affinity for vitamin D binding protein (VDBP) than 1,25-dihydroxyvitamin D; whereas, 1,25-dihydroxyvitamin D has higher affinity for the vitamin D receptor (VDR) than 25-hydroxyvitamin D. HPLC and immunoassays allow the determination of vitamin D status, as measured by 25(OH)D, and 1,25(OH)2D. Recently it has been shown that the vitamin D requirements have been underestimated and that vitamin D2 is much less potent than vitamin D3. Future studies will determine the amount of vitamin D3 necessary for optimal health and well-being.
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This review focuses on the advances made in recent years in the understanding of the multivitamin transporter, a unique and important transporter that transports not one but three different unrelated water-soluble vitamins namely, pantothenate, biotin and lipoate. The transport process mediated by the transporter is active and is energized by the transmembrane sodium ion gradient as well as the membrane potential. The transporter belongs to the sodium-coupled glucose transporter family. The ubiquitous expression of this transporter in mammalian tissues and the fact that it is highly conserved across the species indicate the nutritional relevance and importance of this transporter.
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Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter-mediated drug-drug interactions. The transporters are P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter-mediated drug-drug interaction study is needed. Phenotyping is a methodology that evaluates real-time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.
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