Role In Calcium Absorption Research Articles

Exploring the Interplay between Vitamin D, Insulin Resistance, Obesity and Skeletal Health.

Vitamin D (ViD), plays an important role in calcium absorption and bone mineralization, is associated with bone mineral density. Severe deficiency in ViD has long been linked to conditions such as rickets in children and osteomalacia in adults, revealing its substantial role in skeletal health. Additionally, investigations show an existing interconnection between ViD and insulin resistance (Ins-R), especially in patients with type 2 diabetes mellitus (T2DM). Obesity, in conjunction with Ins-R, may augment the risk of osteoporosis and deterioration of skeletal health. This review aims to examine recent studies on the interplay between ViD, Ins-R, obesity, and their impact on skeletal health, to offer insights into potential therapeutic strategies. Cochrane Library, Google Scholar, and Pubmed were searched to investigate relevant studies until December 2023. Current research demonstrates ViD's impact on pancreatic β-cell function, systemic inflammation, and insulin action regulation. Our findings highlight an intricate association between ViD, Ins-R, obesity, and skeletal health, providing a perspective for the prevention and/or treatment of skeletal disorders in patients with obesity, Ins-R, and T2DM.

Applying data mining techniques to predict vitamin D deficiency in diabetic patients.

Vitamin D is among the vitamins necessary for both adults' and children's health. It plays a significant role in calcium absorption, the immune system, cell proliferation and differentiation, bone protection, skeletal health, rickets, muscle health, heart health, disease pathogenesis and severity, glucose metabolism, glucose intolerance, varying insulin secretion, and diabetes. Because the 25-hydroxyvitamin D (25OHD) test, which is used to measure vitamin D is expensive and may not be covered in healthcare benefits in many countries, this study aims to predict vitamin D deficiency in diabetic patients. The prediction method is based on data mining techniques combined with feature selection by using historical electronic health records. The results were compared with a filter-based feature selection algorithm, namely relief-F. Non-valuable features were eliminated effectively with the relief-F feature selection method without any performance loss in classification. The performances of the methods were evaluated using classification accuracy (ACC), sensitivity, specificity, F1-score, precision, kappa results, and receiver operating characteristic (ROC) curves. The analyses have been conducted on a vitamin D dataset of diabetic patients and the results show that the highest classification accuracy of 97.044% was obtained for the support vector machines (SVM) model using radial kernel that contains 18 features.

Rapid non-genomic actions of 25(OH)D3: state of the art

Over recent years, the secosteroid hormone calcitriol (1α,25(OH)2D3) has been attracting growing attention due to its essential role in calcium absorption and bone mineralization. This hormone elicits these functions through genomic and non-genomic mechanisms. In the former case, the interaction of 1α,25(OH)2D3 with vitamin D receptor (VDR) results in the transcription of genes involved in the regulation of calcium homeostasis. Compared with their genomic counterparts, non-transcriptional effects, on the other hand, occur rapidly and are not subject to the effects of transcription and protein synthesis inhibitors; they have also been shown to be responsible for the multiple actions of vitamin D. The direct precursor metabolite of 1α,25(OH)2D3, calcifediol (25(OH)D3), which also exhibits anti-proliferative and gene regulatory properties, was recently described as an agonistic ligand of VDR, albeit with lower affinity than 1α,25(OH)2D3. This mini-review attempts to offer an overview of the non-genomic actions of calcifediol and the possible mechanisms underlying the generation of these rapid responses. Insights into the rapid non-genomic mechanisms of 25(OH)D3 could help to increase knowledge of the vitamin D endocrine system, and thus result in the identification of novel therapeutic strategies able to regulate non-genomic actions, which could prove crucial in 25(OH)D3 deficiency-related disorders.

Study of Vitamin D2 accumulation potential of two edible mushrooms from North-East India

Vitamin D is a fat-soluble vitamin that plays an important role in calcium absorption from the intestinecontributing to bone health and many other functions leading to health improvement. There are mainlytwo forms of Vitamin D, namely Vitamin D3 (Cholecalciferol) and Vitamin D2 (Ergocalciferol). Ergocalciferol(Vitamin D2) is a form of Vitamin D found in food, especially mushrooms. Mushrooms contain ergosterolin their cell membrane; exposure to sunlight/ultraviolet (UV) light causes a photochemical reaction thatisomerizes ergosterol to Vitamin D2. Mushrooms are extensively grown in North-East India from timeimmemorial by the ethnic people. In this study, Vitamin D2 from fruiting bodies of two Oyster Mushroomspecies, namely Pleurotus florida and Pleurotus cornucopiae, is quantified using a spectrophotometer at 264nm.This study aimed to determine the Vitamin D2 accumulation potential of both the species and to select thebest species with the highest Vitamin D2 accumulation potential. Fresh cultures of P. florida and P. cornucopiaewere maintained in CSIR-North East Institute of Science &Technology (CSIR-NEIST) Mushroom GermplasmUnit, Jorhat, Assam, India and cultivated in the cultivation unit. A total of 24 treatments were given to eachsample by exposing it to UV rays ranging from UV-A (365nm and 395nm) and UV-B (280nm and 310nm)for different time periods. It was observed that Vitamin D2 levels varied with different wavelengths used.In both the species, Vitamin D2 levels increased in the UV-B range than in the UV-A range. Moreover,between the two species under study, P. florida showed the highest Vitamin D2 accumulation potential at280nm when exposed for 120 minutes. The level of Vitamin D2 increased to an optimum level at 120 minutesof UV exposure and then declined upon the increase in the time period. The recommended daily allowanceof Vitamin D is 400-800 IU/day according to WHO. In this study, post-UV treatment, the Vitamin D2 levelsdrastically increased to a range of 1000-6000 IU approximately which is safe and can be used in thepreparation of Vitamin D supplements in future.

Description of Total Vitamin D25-Oh in Toddlers and Children With Developmental Disorders

The age of children is a period in which the process of growth and development takes place. The existence of growth and development disorders in children is a serious problem for both developed and developing countries worldwide. The importance of monitoring growth and development requires adequate nutrition and nutrition, one of which is vitamin D. Vitamin D is a prohormone that plays an important role in the absorption of calcium in the intestine and helps harden bones by regulating the availability of calcium in the blood. This study aims to describe Total Vitamin D 25-OH in toddlers and children with growth and developmental disorders. The research sample was determined by purposive sampling technique based on inclusion and exclusion criteria. The research was conducted at Prodia Kramat Clinical Laboratory in March-April 2021. The D 25-OH level was checked from the patient's serum using the DiaSorin Liaison XL tool. Other variables measured to determine vitamin D status are appetite, eating frequency, nutritional adequacy, consumption of vitamin D supplements, outdoor activity, sunbathing, and genetic and environmental risk factors. Data from the examination of total vitamin D 25-OH levels and vitamin D status of the respondents were analyzed descriptively, then displayed in a table and described. The results showed that most respondents who were examined experienced stunting expected growth and development disorders by 76%, with total vitamin D 25-OH status experiencing insufficiency of 53% .

Vitamin D Target Genes in Dental Health

INTRODUCTION: Vitamin D is an important molecule which plays pivotal role in overall human health and metabolism. This vitamin acts as both vitamin as well as hormone, and thus, dual nature of this vitamin makes it as one of the important chemicals required for the overall health, harmonious growth, and development. Recently, this vitamin is gaining large attention in dentistry, and it is becoming master regulator of dental health. It is well studied that vitamin D plays major role in calcium absorption for bone and teeth mineralisation, it acts as odontogenic inducer of differentiation of human dental pulp cells and in tooth development. STUDY SELECTION, DATA, AND SOURCES: Vitamin D regulates various signalling pathways in dental network and plays a beneficial role. Synthesis of vitamin D takes place in multiple steps in human body. The natural form of vitamin D is fat soluble in nature and is produced in the skin from 7-dehydrocholesterol molecules. Natural Sunlight through its ultraviolet B (UVB) energy converts the precursor7-dehydrocholesterol molecules to vitamin D3. Advanced and unhealthy lifestyle of modern times has led to the deficiency of vitamin D and metabolic syndrome. CONCLUSIONS: Deficiency of vitamin D also leads to various dental problems including dental caries, gingivitis, and periodontal disease. In this short review, we are discussing the role of vitamin D and importance of its target genes in dental health. CLINICAL RELEVANCE: Vitamin D has a major role in managing the oral health this article updates the clinician with the different genes which are responsible for the regulation of vitamin D in different tissues.

34006 Vitamin D deficiency in patients with lichen planopilaris/frontal fibrosing alopecia

Vitamin D has been shown to play an important role in calcium absorption, skin homeostasis, and immune regulation. It is also involved in promoting normal hair follicle growth and cycling. The prevalence of vitamin D deficiency in nonscarring alopecia has been documented. However, the relationship between vitamin D levels and scarring alopecia such as lichen planopilaris/frontal fibrosing alopecia (LPP/FFA) has not been well-studied. This retrospective case series compares the prevalence of vitamin D deficiency in patients with LPP/FFA to that of the general US population.

Abstract 1819: CBP-1008 shows excellent efficacy and desirable drug safety profile in preclinical models

Abstract Folate Receptor Alpha (FRα) is the high affinity folate transporter which is highly expressed in ovarian, lung and breast cancer. Transient Receptor Potential Vanilloid 6(TRPV6), a calcium channel characterized by its high calcium selectivity. It plays an important role in calcium absorption in small intestine and calcium uptake in other epithelial tissues. TRPV6 is also upregulated in breast, ovarian and prostate cancer. CBP-1008, A first-in-class drug conjugate which targets both FRα and TRPV6 with low molecular-weight ligands has been developed. CBP-1008 binds to FRα with high affinity and TRPV6 with low affinity. In presence of TRPV6, CBP-1008 shows faster FRα-mediated internalization and cytotoxicity than it does in absence of TRPV6. Systemic clearance CBP-1008 is observed within 6 hrs. However, the drug retained and accumulated in tumors with a half-life over 48 hrs. As a result, CBP-1008 shows excellent efficacy on tumors with target expression and the response is durable. MTD of CBP-1008 reaches 4 mg/kg in mice, 2 mg/kg in rat and 1 mg/kg in monkey. During the development of molecularly-targeted therapeutics, biomarker assays which can stratify patients and enrich those who respond well to the therapy, play a very critical role. We generated an anti-TRPV6 antibody and developed a first-in-class IHC-based TRPV6 assay. This assay along with an FRα IHC assay have been validated per CAP/CLIA guidelines for patient selection in our clinical trials. Intended indications including ovarian cancer, endometrial cancer, breast, NSCLC and pancreatic cancer. We have evaluated a panel of ovarian PDX models for their biomarker expression and response to CBP-1008 to determine their correlation. It is found that FRα+/TRPV6+ tumor responds better than tumors which have at least one marker negative. Within the FRα+/TRPV6+ tumors, tumor growth inhibition well correlates with IHC score of FRα (R2=0.89). It is indicated that clinical trials in selected indications using biomarkers assay to screening patients will expedite the clinical development of CBP-1008. Initial clinical response has been observed in our Phase I trial. Citation Format: Wei Tan, Wei Wang, Tingting Bu, Xuelian Liu, Yan Teng, Baohua Huang. CBP-1008 shows excellent efficacy and desirable drug safety profile in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1819.

Профілактика дефіциту вітаміну D у дітей. Стан проблеми у світі та Україні

The article presents current data on the prevalence of vitamin D deficiency and criteria for its deficiency in children in different countries. Vitamin D is recognized as one of the most important vitamins involved in many biochemical processes in the body. Its active metabolites play a key role in calcium absorption, bone mineralization and promote phosphate and magnesium metabolism. At the same time, in addition to affecting mineral metabolism, there is a wide range of conditions in which vitamin D also plays a preventive role. Vitamin D has been shown to play a vital role in innate immunity maintenance and is important in prevention of several diseases, including infections, autoimmune diseases, certain forms of cancer, type 1 and 2 diabetes, and cardiovascular diseases. Vitamin D is of particular importance for newborns and young children. This vitamin is involved in important physiological regulatory processes such as bone metabolism, lung development, maturation of the immune system and differentiation of the nervous system. Vitamin D deficiency increases risks of neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, and bronchopulmonary dysplasia. Adequate intake of vitamin D and calcium during childhood can reduce the risk of osteoporosis and other diseases associated with vitamin D deficiency in adults. Recently, vitamin D deficiency has shown to be a potential risk factor for COVID-19 propensity. It has been established that to date most scientific pediatric societies have recognized the need to prevent vitamin D deficiency in healthy children of all ages, but data on the dosage of vitamin D in its prophylactic use differ. Most scientific societies recommend an average of 400–600 IU per day of vitamin D for prophylactic purposes. The analysis of published data shows the need to follow a strategy based on an individual approach, taking into account physiological characteristics, individual requirements and lifestyle. No conflict of interest was declared by the authors. Key words: vitamin D, children, deficiency, prevention.

Histone demethylase KDM6B regulates 1,25-dihydroxyvitamin D3-induced senescence in glioma cells.

Vitamin D is a fat-soluble vitamin and plays an important role in calcium absorption and bone development, whose lack can cause a variety of diseases, including cancer. Human epidemiological studies suggested that vitamin D3 deficiency might increase glioma incidence, but molecular mechanism is less understood. In this study, we show that 1,25-dihydroxyvitamin D3 (the active form of vitamin D3) induces senescence of glioma cells and increases the expression of senescence markers, INK4A and cyclin-dependent kinase inhibitor 1A (CDKN1A). 1,25-Dihydroxyvitamin D3 also upregulates the expression of histone demethylase, KDM6B. Knockdown of KDM6B attenuates 1,25-dihydroxyvitamin D3-induced senescence and upregulation of INK4A and CDKN1A. KDM6B promotes the transcription of INK4A by eliminating the trimethylation of repressive marker H3K27me3 near its promoter. This study reveals a new regulatory mechanism involved in vitamin D3 inhibition on gliomas, which is beneficial to prevention and adjuvant therapy of glioma.

Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults

AimsVitamin D is a fat-soluble vitamin classically known for its role in calcium absorption and bone health. Growing evidence indicates that vitamin D deficiency may be associated with inflammation, insulin resistance, and obesity. However, prior studies examining the association of vitamin D with metabolic risk factors had relatively low representation of individuals of black race, limiting their ability to characterize associations of vitamin D and parameters of metabolic health in black vs. white individuals. MethodsWe examined associations of 25-hydroxyvitamin D (25(OH)D) concentrations with markers of inflammation (interleukin [IL]-6, IL-10, high sensitivity C-reactive protein [hsCRP]), insulin sensitivity (adiponectin, resistin, HOMA-IR), and obesity (body mass index [BMI], waist circumference) in 1042 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a large national cohort of black and white adults 45 years or older. ResultsIn unadjusted analyses, lower 25(OH)D concentrations were associated with higher IL-6 and hsCRP concentrations; lower adiponectin concentrations; higher HOMA-IR; and higher BMI and waist circumference (P < 0.05 for all). After adjustment for sociodemographic, clinical, lifestyle, and laboratory variables, lower 25(OH) D concentrations remained associated with lower adiponectin concentrations, higher IL–6 concentrations, higher HOMA-IR, and higher BMI and waist circumference (P < 0.05 for all). The magnitude of these associations did not differ by race (Pinteraction > 0.1). ConclusionsLower 25(OH)D concentrations are associated with disturbances in metabolic health in both blacks and whites. Whether correcting vitamin D deficiency could offer a beneficial therapy for disease prevention requires further study.

Vitamin D in ocular and systemic health

Accumulated data supports the argument that vitamin D possesses several biological and molecular actions apart from its role in calcium absorption and facilitation of gene expression. Vitamin D deficiency has been an associated risk factor for cardiovascular disease,metabolic syndrome and ocular complications. The aim of this review is to summarise the most relevant data regarding these associations and to try to clarify whether, and to what extent, oral vitamin D supplementation could be used as a beneficial intervention in such diseases.Vitamin D is produced in skin exposed to sunlight UVB radiation and is then metabolised by the kidney into calciferol, which is an active form. The main function of vitamin D is to promote calcium and phosphorus absorption, and studies have shown that a lack of itplays an important role in ocular conditions, such as age-related macular degeneration and diabetic retinopathy. Recent studies have suggested that vitamin D may protect the diabetic retina; however, other vitamin D-associated conditions (diabetes, hypertension and cardiovascular diseases) may result in secondary ocular manifestations and the potential forsight-threatening complications. The purpose of this review is to describe the current literature on the role of vitamin D in ocular and systemic wellness. However, more research is needed to determine if increasing levels of this vitamin can assist in preventing age-related macular degeneration or diabetic retinopathy. Since vitamin D is a circulating steroid hormone, its receptors are found in almost every cell in the human body, and this suggests that vitamin D might have a very broad role for overall health. However, there is still demand for further research to clarify the clinical use of vitamin D in the prevention and treatment of various chronic diseases.

PO-0078 The Relationship Between Maternal And Neonatal 25(oh) Vitamin D Status

Background In this study we aimed to investigate the relationship between maternal and neonatal 25(OH)D levels. Methods The subjects were 58 mothers and their newborns who were born between February 2012 and April 2012. Blood specimens were obtained within 72 h of birth and from mothers. Serum 25(OH)D concentrations were measured. Vitamin D deficiency was defined as serum concentrations ≤20 ng/mL. Results The mean gestational age and birth weight of preterm infants were 33.06 ± 2.2 weeks and 2125.4 ± 546 g and for term infants were 38.84 ± 1 weeks and 3470.3 ± 451 g, respectively. Sociodemographic characteristics of mothers were not significantly different between groups. Twelve percent of infants born before 32 completed weeks, 16% infants born between 32–36 weeks and 28% of term infants had vitamin D deficiency. Vitamin D deficiency was found in 27% mothers of preterm infants and 42% mothers of term infants. Conclusion Vitamin D receptors plays an important role in calcium absorption and bone metabolism. In the literature there are reports that vitamin D deficiency during pregnancy had adverse gestational outcomes including risk of pre-eclampsia, gestational diabetes. The mean vitamin D levels were normal in infants whereas their mothers had low levels of vitamin D. When we consider that all mothers in the study received vitamin D supplements, we should give appropriate vitamin D prophylaxis during pregnancy. Also we should give adequate vitamin D supplementation to the infants without any delay.

Factors Associated with Calcium Absorption in Postmenopausal Women: A Post Hoc Analysis of Dual-Isotope Studies

Reduced calcium absorption is a risk factor for osteoporosis. This study examined factors associated with fractional calcium absorption (FCA) and net calcium absorption in postmenopausal women in a post hoc analysis of three completed dual-isotope studies. Data were analyzed from 50 postmenopausal women undergoing 121 inpatient research visits in three studies evaluating changes in FCA related to correction of vitamin D insufficiency (n=19), use of proton pump inhibitors (n=21), and use of aromatase inhibitors to treat breast cancer (n=10). Net calcium absorption was the product of FCA and total calcium intake in milligrams per day. Variables included subjects' age, race, body mass index, serum calcium, creatinine, parathyroid hormone, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and habitual intake of kilocalories, protein, fat, carbohydrate, fiber, calcium, iron, magnesium, oxalate, phosphorus, potassium, and vitamin D based on outpatient diet diaries. In multivariate models, subjects' age, dietary intake of kilocalories, carbohydrates, fat, fiber, calcium, and potassium were significant predictors of FCA. In multiple variable models predicting net calcium absorption, dietary intake of kilocalories, fat, fiber, calcium, potassium, and serum 1,25-dihydroxyvitamin D were significant. The square of the correlation between actual and predicted values (an approximation of R2) was 0.748 for FCA and 0.726 for net calcium absorption. Similar to other studies, this study found that age, 1,25-dihydroxyvitamin D, and dietary calcium and fat were associated with calcium absorption. Dietary intake of kilocalories, carbohydrates, and potassium were new factors that were significantly associated with FCA and net calcium absorption. In summary, the study suggests that several dietary habits play a role in calcium absorption, beyond vitamin D and calcium.

Vitamin D in allergic disease: Shedding light on a complex problem

Vitamin D is unique among nutritional factors because the intake of this special vitamin represents the sum of vitamin D obtained from diet, nutritional supplements, and endogenous production after exposure to sunlight. The current recommended nutritional intake requirements reflect needs based on its established role in calcium absorption and bone health. However, recent studies have revealed that vitamin D has important functions in the immune system and might influence the course of immune-mediated disorders, including atopic dermatitis and asthma. This review discusses the scientific rationale for a role for vitamin D in immune function, gives an update on allergic disease associations with lower vitamin D serum levels, and discusses recent observations relating to vitamin D in immune function.

A Novel Glycosylphosphatidylinositol-Anchored Alkaline Phosphatase Dwells in the Hepatic Duct of the Pearl Oyster, Pinctada fucata

Alkaline phosphatases are ubiquitous enzymes involved in many important biological processes. Mammalian tissue-nonspecific alkaline phosphatase (TNAP) has long been thought to play an important role in bone mineralization. In this study, we identified a full-length cDNA encoding a potential alkaline phosphatse from pearl oyster Pinctada fucata by RT-PCR and RACE and designated the encoded protein as PFAP. The sequence of PFAP shares an overall similarity of 67% with that of human TNAP. Prediction and analysis of its secondary and tertiary structure revealed that the PFAP contains two mammalian-specific regions, the crown domain, involved in collagen binding, and the calcium binding domain, which hint its potential ability to participate in biomineralization. RT-PCR and in situ hybridization showed that the PFAP mRNA distributes specifically in the hepatic duct of the digestive diverticula. These findings implied its possible role in calcium absorption and transportation. In vivo, PFAP could be specifically released by phosphatidylinositol-specific phospholipase C (PIPLC), suggesting it is glycophosphatidylinositol-anchored to the plasma membrane. Therefore, a human growth hormone-PFAP fusion was constructed to locate the cleavage/attachment site. Immunofluorescent labeling and immunoblotting showed that Asn-477 is the cleavage/attachment site and the 25-residue peptide COOH-terminal to Asn-477 is removed during glycophosphatidylinositol anchoring. This research will hopefully pave the way to illustrate the role PFAP plays in calcium transportation related to pearl biomineralization.

Inulin and fructo-oligosaccharides differ in their ability to enhance the density of cancellous and cortical bone in the axial and peripheral skeleton of growing rats

Although dietary fructans improve calcium absorption and bone mineral content (BMC) in rats, their effect on calcium bioavailability and bone density may vary with their degree of polymerization. Therefore, for a 3-month period, growing rats received either a control diet or a diet enriched with either oligofructose (OLF) or inulin. At sacrifice, body weight, lean body mass and appendicular bone length were similar in the 3 groups. Rats fed fructans had a similar increase in cecal wall weight (30%), but the relative increase in cecal levels of calbinding-9 K was 2 in the OLF group and 4 in the inulin group. Further, the significant decrease in serum levels of type I collagen C-telopeptide was greater in the inulin group (30%) than in the OLF group (16%). The increase in whole-body bone mineral content (BMC) as measured by DXA was greater in the inulin group than in the OLF group but DXA detected an increase in the BMC of excised femurs only in the inulin group. In contrast, pQCT conducted ex vivo detected a significant increase in the area and mineral density (BMD) of the cancellous bone of both the proximal tibia and vertebra in rats fed fructans and the effect of inulin was greater ( P < 0.01) than that of OLF ( P < 0.05). Further, inulin but not OLF significantly enhanced the BMD of the cortical bone in both appendicular and peripheral sites ( P < 0.01) as well as the polar stress/strain index of femurs ( P < 0.01). These observations suggest that, although both inulin and OLF both have a positive effect on BMD, the greatest effect of inulin is related to the higher capacity of this fructan to reduce bone resorption. The different anti-resorptive capacity of the 2 fructans might be related to their different impact on calcium absorption and bioavailability since the increase in cecal amounts of calbindin-9 K, a protein known to play an important role in calcium absorption, was greater in rat fed inulin than in rats fed OLF. Although cecal wall hyperplasia may be of concern, it remains to establish whether the positive effect of fructans observed on calcium absorption in humans is also associated with a positive effect on bone mass and/or mineral density.

Mechanisms of calcium transport in human colonic basolateral membrane vesicles.

Human colon has been suggested to play an important role in calcium absorption especially after extensive disease or resection of the small intestine. We have previously demonstrated the presence of a carrier-mediated calcium uptake mechanism in the human colonic luminal membrane vesicles. Current studies were, therefore, undertaken to investigate the mechanism(s) of calcium exit across the basolateral membrane domain of the human colon. Human colonic basolateral membrane vesicles (BLMVs) were isolated and purified from mucosal scrapings of organ donor colons, utilizing a technique developed in our laboratory. 45Ca uptake was measured by a rapid filtration technique. 45Ca uptake represented transport into the intravesicular space as evidenced by an osmolarity study and by the demonstration of Ca2' efflux from calcium preloaded vesicles by Ca2+ ionophore A23187. Calcium uptake was stimulated by Mg2+ ATP. The kinetic parameters for ATP-dependent Ca2+ uptake revealed saturation kinetics with Michaelis constant (Km) of 0.22 +/- 0.04 microM and a maximum rate of uptake (Vmax) of 0.38 +/- 0.12 nmol/mg protein/min. The Km of ATP concentration required for half maximal Ca2+ uptake was 0.39 +/- 0.04 mM. ATP-stimulated calcium uptake into these vesicles was further stimulated in the presence of calmodulin and was inhibited by calmodulin antagonist, trifluoperazine. Uptake of 45Ca into BLMVs was markedly inhibited by cis-Na+ but was significantly stimulated by trans-Na+ (40-50% stimulation). Our results demonstrate the presence of a Mg2+/ATP-dependent calmodulin-regulated Ca2+ transport system and a Na+-Ca2+ exchange process in the human colonic basolateral membranes.

A proposed cellular mechanism for calcium transport in the intestinal epithelial cell

Intracellular transport of calcium from the apical to the basal-lateral region of the intestinal epithelial cell was investigated in duodenum from normal fed, fasted, and calcium-loaded rats. The process was followed with time using electron microscopy with potassium pyroantimonate to precipitate calcium. The observations made were subjected to morphometric analysis. The specificity of the method was demonstrated in the villus cell by resistance to microincineration and by absence of deposits following exposure to EGTA. Using this method calcium was seen in cells from calcium-fed rats at the microvillus border, in the Golgi zone, and within the internal compartments of the mitochondria. In cells from fasted rats calcium was not seen. Mitochondria were found largely at the apex of the cell and were free of detectable calcium. By 5 min, in the cells of fasted rats given a calcium load, the calcium had reached the Golgi apparatus and the inner mitochondrial compartment. After 15 min mitochondria were heavily loaded with calcium and had moved to the basal region of the cell. These observations suggest that mitochondria play an important role in absorption of calcium and appear to transport this ion from the apex to the basal region of the cell where entry into the capillaries takes place.

Relationship of calcium uptake and calcium-binding protein synthesis in chick and rat intestine in response to Solanum malacoxylon

It now seems clear that one of the ways by which vitamin D affects calcium absorption is by the stimulation of the de novo synthesis of calcium-binding protein [l-3]. How calcium-binding protein acts to promote calcium absorption is still a matter for discussion, but the correlation between vitamin D-stimulated calcium absorption and the production of calcium-binding protein is such that the protein must play an intimate part in this process [3,4]. To determine whether calcium-binding protein plays an obligatory role in calcium absorption the effect has been studied of other substances capable of changing calcium absorption, to see if there is always a corresponding change in the level of calcium-binding protein. Experiments of this nature have so far produced conflicting results. Nicarbazin for instance has been shown to inhibit both calcium-binding protein levels and egg formation in the hen [5] but cortisone, given with vitamin D to rachitic chicks, inhibits the action of vitamin D on calcium absorption without affecting the vitamin D-dependent synthesis of calcium-binding protein [6]. Another agent, capable of changing calcium metabolism in different animals, has recently been found in the leaves of the shrub Solanum malacoxylon. Used in the dried form or as an extract, active principles in the leaf act to raise plasma calcium and phosphate levels and to increase calcium absorption [7-lo]. It has been claimed that the effect of the