Evidence for an interaction of insulin and sex steroids in the regulation of vitamin D metabolism in the rat

1987 ◽  
Vol 115 (2) ◽  
pp. 295-301 ◽  
Author(s):  
B. L. Nyomba ◽  
R. Bouillon ◽  
P. De Moor
Keyword(s):  
Vitamin D ◽  
Diabetic Rats ◽  
Vitamin D Metabolites ◽  
Serum Concentrations ◽  
Insulin Deficiency ◽  
Intact Male ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D ◽  
Androgen Withdrawal ◽  
Intact Rats

ABSTRACT Vitamin D metabolites and vitamin D-binding protein (DBP) were measured in non-diabetic rats and in rats made diabetic with streptozotocin. The animals were studied in the intact state, after gonadectomy and during pregnancy. In male non-diabetic rats the serum concentrations of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and DBP decreased after orchidectomy and were restored by treatment with testosterone. In female non-diabetic rats, these parameters increased after ovariectomy. Increased 1,25-(OH)2D3 and decreased DBP concentrations were found during pregnancy in non-diabetic rats. After the induction of diabetes in intact rats of both sexes, the concentration of DBP decreased, but a significant decrease in the concentration of 1,25-(OH)2D3 was found in male animals only. After ovariectomy, however, 1,25-(OH)2D3 decreased also in female diabetic rats. Both orchidectomy and insulin deficiency depressed serum concentrations of 1,25-(OH)2D3 (−22 and −45% respectively) and DBP (−14 and −29% respectively), but the effects of insulin deficiency were greater than those of androgen withdrawal. Moreover, the testosterone concentration was twofold lower in intact male diabetic rats than in non-diabetic animals. Insulin, but not testosterone treatment, however, restored DBP and 1,25-(OH)2D3 concentrations in diabetic rats, and insulin was effective in intact as well as in gonadectomized animals. This study shows that insulin deficiency decreases the concentrations of DBP and 1,25-(OH)2D3 in the rat, and that these decreases are facilitated by androgens, but counteracted by oestrogens. J. Endocr. (1987) 115, 295–301

Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites

1983 ◽  
Vol 104 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Kinsuke Tsuda ◽  
Jiro Takemura ◽  
Sigeo Nishi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Diabetic Rats ◽  
Plasma Vitamin ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Plasma Urea ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Streptozotocin Induced Diabetes ◽  
25 Hydroxyvitamin D

Abstract. In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-hydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.

Effects of insulin on altered mineral and vitamin D metabolism in streptozotocin-induced diabetes

1985 ◽  
Vol 108 (2) ◽  
pp. 231-236 ◽  
Author(s):  
Hitoshi Ishida ◽  
Yutaka Seino ◽  
Shigeo Nishi ◽  
Norikazu Kitano ◽  
Michiyo Seno ◽  
...  
Keyword(s):  
Vitamin D ◽  
Insulin Therapy ◽  
Diabetic Rats ◽  
Plasma Calcium ◽  
Diabetic Group ◽  
Ionized Calcium ◽  
Control Group ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D

Abstract. In order to ascertain whether or not abnormal mineral and vitamin D metabolism in diabetes can be reversed by insulin therapy, plasma calcium, ionized calcium, phosphorus, parathyroid hormone (PTH) and vitamin D metabolites were measured in control, streptozotocin (STZ) diabetic and insulin-treated diabetic rats. Blood glucose levels in diabetic rats treated with insulin decreased to normal. The low plasma calcium and ionized calcium levels in diabetic rats were found to be normal in insulin-treated diabetic rats. An elevated PTH level was observed in the diabetic group, but it was at normal levels in the insulin-treated diabetic group. Plasma 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) in the diabetic group were decreased compared to those in control rats, but these were also fully restored to control levels by insulin therapy. However, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) levels in the untreated diabetic group tended to be lower than in controls, and the values in insulin-treated rats were significantly decreased compared to the control group. The ratio of 1,25(OH)2D to 25(OH)D in diabetic rats was higher than in controls, but it was decreased after insulin therapy and was significantly lower than in the control group. It is suggested, therefore, that the negative calcium balance and decreased 25(OH)D and 24,25(OH)2D levels are derived from the metabolic derangement due to the insulin deficiency. Furthermore, insulin seems to suppress the conversion of 25(OH)D to 1,25(OH)2D in experimental diabetes in vivo.

scholarly journals Vitamin D Measurement, the Debates Continue, New Analytes Have Emerged, Developments Have Variable Outcomes

2019 ◽  
Vol 106 (1) ◽  
pp. 3-13 ◽  
Author(s):  
William D. Fraser ◽  
Jonathan C. Y. Tang ◽  
John J. Dutton ◽  
Inez Schoenmakers
Keyword(s):  
Vitamin D ◽  
Quality Assurance ◽  
Measurement Procedure ◽  
Vitamin D Metabolites ◽  
Experimental Conditions ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Target Values ◽  
Analytical Approaches

AbstractThe demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments of immunoassays have changed the landscape. Programmes and materials for assay standardisation, harmonisation and the expansion of the vitamin D external quality assurance scheme (DEQAS) with the provision of target values as measured by a reference measurement procedure have improved standardisation, quality assurance and comparability of measurements. In this article, we describe developments in the measurement of the commonly analysed vitamin D metabolites in clinical and research practice. We describe current analytical approaches, discuss differences between assays, their origin, and how these may be influenced by physiological and experimental conditions. The value of measuring metabolites beyond 25 hydroxyvitamin D (25(OH)D), the marker of vitamin D status, in routine clinical practice is not yet confirmed. Here we provide an overview of the value and application of the measurement of 1,25 dihydroxyvitamin D, 24,25 dihydroxyvitamin D and free 25OHD in the diagnosis of patients with abnormalities in vitamin D metabolism and for research purposes.

scholarly journals Association of Differing Qatari Genotypes with Vitamin D Metabolites

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Youssra Dakroury ◽  
Alexandra E. Butler ◽  
Soha R. Dargham ◽  
Aishah Latif ◽  
Amal Robay ◽  
...  
Keyword(s):  
Vitamin D ◽  
Skin Pigmentation ◽  
Genetic Differences ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Objective. Genetic studies have identified four Qatari genotypes: Q1 Arab, Bedouin; Q2 Asian/Persian; Q3 African; and a fourth admixed group not fitting into the previous 3 groups. This study was undertaken to determine if there was an increased risk of deficiency of vitamin D and its metabolites associated with differing genotypes, perhaps due to genetic differences in skin pigmentation. Methods. 398 Qatari subjects (220 type 2 diabetes and 178 controls) had their genotype determined by Affymetrix 500 k SNP arrays. Total values of 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 25-hydroxy-3epi-vitamin D (3epi-25(OH)D) concentrations were measured by the LC-MS/MS analysis. Results. The distribution was as follows: 164 (41.2%) genotyped Q1, 149 (37.4%) genotyped Q2, 31 (7.8%) genotyped Q3, and 54 (13.6%) genotyped “admixed.” Median levels of 25(OH)D and 3epi-25(OH)D did not differ across Q1, Q2, Q3, and “admixed” genotypes, respectively. 1,25(OH)2D levels were lower (p<0.04) between Q2 and the admixed groups, and 24,25(OH)2D levels were lower (p<0.05) between Q1 and the admixed groups. Vitamin D metabolite levels were lower in females for 25(OH)D, 1,25(OH)2D (p<0.001), and 24,25(OH)2D (p<0.006), but 3epi-25(OH)D did not differ (p<0.26). Diabetes prevalence was not different between genotypes. Total 1,25(OH)2D (p<0.001), total 24,25(OH)2D (p<0.001), and total 3epi-25(OH)D (p<0.005) were all significantly lower in diabetes patients compared to controls whilst the total 25(OH)D was higher in diabetes than controls (p<0.001). Conclusion. Whilst 25(OH)D levels did not differ between genotype groups, 1,25(OH)2D and 24,25(OH)2D were lower in the admixed group, suggesting that there are genetic differences in vitamin D metabolism that may be of importance in a population that may allow a more targeted approach to vitamin D replacement. This may be of specific importance in vitamin D replacement strategies with the Q2 genotype requiring less, and the other genotypes requiring more to increase 1,25(OH)2D. Whilst overall the group was vitamin D deficient, total 25(OH)D was higher in diabetes, but 1,25(OH)2D, 24,25(OH)2D, and 3epi-25(OH)D were lower in diabetes that did not affect the relationship to genotype.

scholarly journals Simple Fast Quantification of Cholecalciferol, 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D in Adipose Tissue Using LC-HRMS/MS

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1977 ◽  
Author(s):  
Laurianne Bonnet ◽  
Marielle Margier ◽  
Ljubica Svilar ◽  
Charlene Couturier ◽  
Emmanuelle Reboul ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Solid Phase ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Relative Standard ◽  
The Impact

Vitamin D metabolism is actively modulated in adipose tissue during obesity. To better investigate this process, we develop a specific LC-HRMS/MS method that can simultaneously quantify three vitamin D metabolites, i.e., cholecalciferol, 25-hydroxyvitamin D3 (25(OH)D3), and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in a complex matrix, such as mouse adipose tissue and plasma. The method uses pretreatment with liquid–liquid or solid–phase extraction followed by derivatization using Amplifex® reagents to improve metabolite stability and ionization efficiency. Here, the method is optimized by co-eluting stable isotope-labelled internal standards to calibrate each analogue and to spike biological samples. Intra-day and inter-day relative standard deviations were 0.8–6.0% and 2.0–14.4%, respectively for the three derivatized metabolites. The limits of quantification (LoQ) achieved with Amplifex® derivatization were 0.02 ng/mL, 0.19 ng/mL, and 0.78 ng/mL for 1,25(OH)2D3, 25(OH)D3 and cholecalciferol, respectively. Now, for the first time, 1,25(OH)2D3 can be co-quantified with cholecalciferol and 25(OH)D3 in mouse adipose tissue. This validated method is successfully applied to study the impact of obesity on vitamin D status in mice.

Vitamin D Metabolism in Patients Intoxicated with Ergocalciferol

1985 ◽  
Vol 68 (2) ◽  
pp. 135-141 ◽  
Author(s):  
E. Barbara Mawer ◽  
J. T. Hann ◽  
Jacqueline L. Berry ◽  
M. Davies
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Calcium Concentration ◽  
Mass Action ◽  
Vitamin D Metabolites ◽  
Serum Concentrations ◽  
High Concentration ◽  
Vitamin D Metabolism ◽  
Serum Calcium Concentration ◽  
Per Se

1. Vitamin D metabolites were measured on admission in eight patients intoxicated with ergocalciferol (serum calcium 3.01-4.05 mmol/l) and also during the subsequent 2 months in six of the eight. 2. Serum concentrations of 25-hydroxyergocalciferol, on admission, were grossly elevated in all patients (range 583-1843 nmol/l). 3. Serum calcium concentration was related significantly only to the concentration of 25-hydroxyergocalciferol (P = 0.003). 4. Concentrations of 25-hydroxyergocalciferol in serum were significantly related to those of calciferol (P = 0.004). 5. Elevated initial concentrations of 1,25-dihydroxycalciferol, mainly as 1,25-dihydroxyergocalciferol, were found in seven of the eight patients (range 179-313 pmol/l). 6. It is suggested that the hypercalcaemia in these patients may be explained by the action of 25-hydroxyergocalciferol at high concentration in competing for 1,25-dihydroxycalciferol receptors, thus exerting a biological effect per se, and also by increasing the synthesis of 1,25-dihydroxycalciferol through a mass-action effect on the renal 1α-hydroxylase.

Serum levels of vitamin D metabolites in the elderly

1989 ◽  
Vol 121 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Lage Aksnes ◽  
Ole Rødland ◽  
Ole R. Ødegaard ◽  
Kåre J. Bakke ◽  
Dagfinn Aarskog
Keyword(s):  
Vitamin D ◽  
Geriatric Patients ◽  
Vitamin D Supplementation ◽  
Vitamin D Metabolites ◽  
Serum Concentrations ◽  
Geriatric Ward ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Elderly Living ◽  
At Home

Abstract. The serum concentrations of 25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D-binding protein, PTH and calcitonin were measured in three groups of elderly Norwegian subjects (age 70–96 years): active elderly living at home, warded geriatric patients not supplemented with vitamin D, and warded geriatric patients supplemented with a daily dose of 400 IU vitamin D2. The results were compared with the concentrations of vitamin D metabolites found in a group of young and middle-aged adults (age 22–59 years). Decreased serum concentrations of 25-dihydroxyvitamin D3 were found in all groups of elderly compared with younger adults. Active elderly living at home had higher concentrations of 25-dihydroxyvitamin D3 than geriatric ward patients. Supplementation of geriatric ward patients with 400 IU vitamin D2 resulted in an increase in the median serum 25-dihydroxyvitamin D concentration by about 30 nmol/l. Decreased median concentration of 1,25-dihydroxyvitamin D was found in geriatric ward patients not supplemented with vitamin D, indicating that this group is at risk of vitamin D deficiency. The active elderly living at home and the warded geriatric patients receiving vitamin D supplementation had normal median concentrations of 1,25-dihydroxyvitamin D, indicating that nephrogenous synthesis of 1,25-dihydroxyvitamin D is not generally impaired in the elderly, and that a moderate vitamin D supplementation may correct low 1,25-dihydroxyvitamin D levels owing to vitamin D deficiency. However, the serum concentrations of 1,25-dihydroxyvitamin D showed great individual variations. No significant differences were observed for vitamin D-binding protein, 'free-1,25-dihydroxyvitamin D' or PTH between the groups. The median serum concentrations of 24,25-dihydroxyvitamin D were significantly lower in all three groups of elderly compared with the younger adults.

Vitamin D metabolism in the Damara mole-rat is altered by exposure to sunlight yet mineral metabolism is unaffected

1994 ◽  
Vol 143 (2) ◽  
pp. 367-374 ◽  
Author(s):  
T Pitcher ◽  
I N Sergeev ◽  
R Buffenstein
Keyword(s):  
Vitamin D ◽  
Mineral Metabolism ◽  
Plasma Concentrations ◽  
Sun Exposure ◽  
Inorganic Phosphorus ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Highly Efficient

Abstract Vitamin D may be endogenously synthezised in the skin in the presence of sunlight or, alternatively, acquired from dietary sources. Cryptomys damarensis appear to have a naturally impoverished vitamin D status with low plasma concentrations of both 25-hydroxyvitamin D (25(OH)D; <5 ng/ml) and 1,25-dihydroxyvitamin D (1,25(OH)2D; <20 pg/ml). We attribute this to their underground habitat and herbivorous habits. We questioned whether these subterranean mammals could utilize sunlight-mediated pathways and therefore compared vitamin D metabolism and function when animals were (a) housed naturally (control), (b) given an oral vitamin D3 (D3) supplement (1 IU/g dry matter food eaten per day) and (c) exposed to 10 h of sunlight. Control animals exhibited a highly efficient apparent fractional absorption of both calcium (Ca) and inorganic phosphorus (Pi) (>90%), passive mode of intestinal mineral uptake, yet tightly regulated serum ionized calcium (Ca2+). The ratio of 25(OH)D-1α-hydroxylase (1-OHase) to 25(OH)D-24R-hydroxylase (24-OHase) activity in the kidney, corresponded with a state of vitamin D deficiency. Cryptomys damarensis responded to both oral D3 supplementation and sun exposure by an increase in plasma concentration of 1,25(OH)2D with a commensurate decline (P<0·05) in 1-OHase activity, and a resulting decrease (P<0·05) in the ratio of 1-OHase:24-OHase activity. Despite these changes, the intestinal mode of Ca uptake and plasma total Ca, Ca2+ and Pi remained unchanged with either treatment. Responses to sunlight were less pronounced than that of oral D3 supplementation. These data confirm that naturally vitamin D-deficient mole-rats can convert vitamin D to the active hormone 1,25(OH)2D, and indicate that mole-rats function optimally at the low concentrations of vitamin D metabolites found naturally. Furthermore, these animals exhibit a highly efficient vitamin D-independent mode of intestinal Ca absorption. Journal of Endocrinology (1994) 143, 367–374

Growth hormone increases serum 1,25-dihydroxyvitamin D levels and decreases 24,25-dihydroxyvitamin D levels in children with growth hormone deficiency

1997 ◽  
Vol 136 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Shi Wei ◽  
Hiroyuki Tanaka ◽  
Toshihide Kubo ◽  
Taeko Ono ◽  
Susumu Kanzaki ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Vitamin D ◽  
Renal Tubules ◽  
Vitamin D Metabolites ◽  
Gh Therapy ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Igf I ◽  
Phosphorus Levels

Abstract The influence of growth hormone (GH) on calcium–phosphorus metabolism and modulation of vitamin D metabolism has been demonstrated, but the mechanism remains unclear. We investigated the effect of a 6-month course of GH therapy on vitamin D and mineral metabolism in twelve GH-deficient children. Before GH therapy, levels of vitamin D metabolites and other biochemistry data were within normal ranges. All patients responded to GH therapy with increased growth velocity. 1,25-Dihydroxyvitamin D levels increased after 1 month of treatment and remained at these higher levels, with a significant increase found at 3 months (P < 0·05), whereas 24,25-dihydroxyvitamin D levels were decreased at 1 and 3 months, the latter being a significant decrease (P < 0·05), and then returned to the baseline levels at 6 months. 25-Hydroxyvitamin D levels did not change significantly. A significant increase in serum insulin-like growth factor-I (IGF-I) levels occurred during the 6 months of treatment (1 month, P < 0·01; 3 and 6 months, P < 0·001). Serum parathyroid hormone (PTH) levels decreased significantly at 3 and 6 months (3 months, P < 0·01; 6 months, P < 0·05). Serum calcium and phosphorus levels did not change significantly. Significant increases were found in the urinary calcium/urinary creatinine ratio (3 and 6 months, P < 0·05) and the percent tubular reabsorption of phosphorus levels (1 and 3 months, P 0·05). The results of this study confirmed the actions of GH on renal tubules with increases in calcium excretion and phosphorus reabsorption, and indicate that the action of GH on modulating vitamin D metabolism may be IGF-I mediated, not PTH mediated. European Journal of Endocrinology 136 45–51

Vitamin D metabolites in diabetic patients: Decreased serum concentration of 24,25-dihydroxyvitamin D

1982 ◽  
Vol 42 (6) ◽  
pp. 487-491 ◽  
Author(s):  
Claus Christiansen ◽  
Merete Sanvig Christensen ◽  
Peter McNair ◽  
Britta Nielsen ◽  
Steen Madsbad
Keyword(s):  
Vitamin D ◽  
Serum Concentration ◽  
Diabetic Patients ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D
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