Browsing by Subject "vitamin D"

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    1,25-Dihydroxyvitamin D3 enhances glucose-stimulated insulin secretion in mouse and human islets: a role for transcriptional regulation of voltage-gated calcium channels by the vitamin D receptor
    (Elsevier, 2018) Kjalarsdottir, Lilja; Tersey, Sarah A.; Vishwanath, Mridula; Chuang, Jen-Chieh; Posner, Bruce A.; Mirmira, Raghavendra G.; Repa, Joyce J.; Pediatrics, School of Medicine
    Aim Vitamin D deficiency in rodents negatively affects glucose-stimulated insulin secretion (GSIS) and human epidemiological studies connect poor vitamin D status with type 2 diabetes. Previous studies performed primarily in rat islets have shown that vitamin D can enhance GSIS. However the molecular pathways linking vitamin D and insulin secretion are currently unknown. Therefore, experiments were undertaken to elucidate the transcriptional role(s) of the vitamin D receptor (VDR) in islet function. Methods Human and mouse islets were cultured with vehicle or 1,25-dihydroxyvitamin-D3 (1,25D3) and then subjected to GSIS assays. Insulin expression, insulin content, glucose uptake and glucose-stimulated calcium influx were tested. Microarray analysis was performed. In silico analysis was used to identify VDR response elements (VDRE) within target genes and their activity was tested using reporter assays. Results Vdr mRNA is abundant in islets and Vdr expression is glucose-responsive. Preincubation of mouse and human islets with 1,25D3 enhances GSIS and increases glucose-stimulated calcium influx. Microarray analysis identified the R-type voltage-gated calcium channel (VGCC) gene, Cacna1e, which is highly upregulated by 1,25D3 in human and mouse islets and contains a conserved VDRE in intron 7. Results from GSIS assays suggest that 1,25D3 might upregulate a variant of R-type VGCC that is resistant to chemical inhibition. Conclusion These results suggest that the role of 1,25D3 in regulating calcium influx acts through the R-Type VGCC during GSIS, thereby modulating the capacity of beta cells to secrete insulin.
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    Bone Turnover is not Influenced by Serum 25-Hydroxyvitamin D in Pubertal Healthy Black and White Children
    (Elsevier B.V., 2012-10) Hill, Kathleen M.; Laing, Emma M.; Hausman, Dorothy B.; Acton, Anthony; Martin, Berdine R.; McCabe, George P.; Weaver, Connie M.; Lewis, Richard D.; Peacock, Munro; Department of Medicine, IU School of Medicine
    Low serum 25-hydroxyvitamin D [25(OH)D] is common in healthy children particularly in blacks. However, serum 25(OH)D concentrations for optimal bone turnover in children is unknown and few data exist that describe effects of increasing serum 25(OH)D on bone turnover markers during puberty. The purpose of this study was to determine the relationships between serum 25(OH)D and changes in serum 25(OH)D and bone turnover in white and black pubertal adolescents. Bone turnover markers were measured in 318 healthy boys and girls from Georgia (34°N) and Indiana (40°N) who participated in a study of oral vitamin D3 supplementation (0 to 4000 IU/d). Serum 25(OH)D, osteocalcin, bone alkaline phosphatase, and urine N-telopeptide cross-links were measured at baseline and 12 weeks. Relationships among baseline 25(OH)D and bone biomarkers, and between changes over 12 weeks were determined and tested for effects of race, sex, latitude, and baseline 25(OH)D. Median 25(OH)D was 27.6 ng/mL (n=318, range 10.1–46.0 ng/mL) at baseline and 34.5 ng/mL (n=302, range 9.7–95.1 ng/mL) at 12 weeks. Neither baseline nor change in 25(OH)D over 12 weeks were associated with bone turnover. The lack of association was not affected by race, sex, latitude, or baseline serum 25(OH)D. Serum 25(OH)D in the range of 10-46 ng/mL appears to be sufficient for normal bone turnover in healthy black and white pubertal adolescents.
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    Pre-pregnancy habitual intake of vitamin D from diet and supplements in relation to risk of gestational diabetes mellitus: a prospective cohort study
    (Wiley, 2017) Bao, Wei; Song, Yiqing; Bertrand, Kimberly A.; Tobias, Dierdre K.; Olsen, Sjurdur F.; Chavarro, Jorge E.; Mills, James L.; Hu, Frank B.; Zhang, Cuilin; Epidemiology, School of Public Health
    Background Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the impact of vitamin D intake either from diet or from supplements on the development of gestational diabetes mellitus (GDM) remains unknown. We prospectively examined the association of pre-pregnancy habitual intake of vitamin D from diet and supplements with risk of incident GDM in a well-established cohort. Methods We included 21,356 singleton pregnancies from 15,225 women in the Nurses' Health Study II cohort. Diet information, including vitamin D intakes from food sources and supplements, was assessed in 1991 and every four years thereafter by validated food frequency questionnaires. We used log-binomial models with generalized estimating equations to estimate the relative risks (RRs) and 95% confidence intervals (CIs). Results We documented 865 incident GDM cases during 10 years of follow-up. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1–399, ≥ 400 IU/d were 1.00 (reference), 0.80 (0.67-0.96), and 0.71 (0.56-0.90), respectively (P for trend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. Conclusions Pre-pregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. Our study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.
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    Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone
    (Bone, 2014-12-04) Saito, Mitsuru; Grynpas, Marc D.; Burr, David B.; Allen, Matthew R.; Smith, Susan Y.; Doyle, Nancy; Amizuka, Norio; Hasegawa, Tomoka; Kida, Yoshikuni; Marumo, Keishi; Saito, Hitoshi
    Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0mg/mL) and low-density (<2.0mg/mL) fractions from the ELD-treated groups than in the corresponding fractions in the OVX-vehicle control groups. On the other hand, non-enzymatic crosslinks were lower in both the high- and low-density fractions. These observations indicated that ELD treatment stimulated the enzymatic reaction of collagen crosslinks and bone mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage, and non-enzymatic collagen crosslinks all increase. Bone anabolic agents such as parathyroid hormone decrease bone mineralization and bone microdamage by stimulating bone remodeling. ELD did not fit into either category. Histological analysis indicated that the ELD treatment strongly suppressed bone resorption by reducing the number of osteoclasts, while also stimulating focal bone formation without prior bone resorption (bone minimodeling). These bidirectional activities of ELD may account for its unique effects on bone quality.