The Stimulation of 1,25-Dihydroxycholecalciferol Metabolism in Vitamin D-deficient Rats by 1,25-Dihydroxycholecalciferol Treatment

Frolik, Charles A.; DeLuca, Hector F.

doi:10.1172/jci107214

Cited by 60 publications

(12 citation statements)

References 26 publications

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“…In the case of glucose, using a tracer dose of [ 14 C] glucose, Zilversmit (1960) observed that the fractional turnover rate for blood glucose in humans was 0·1/h and the pool size 5 g. When 50 g glucose was administered intravenously the turnover rate was 1·0/h, a 10-fold increase (Karam et al 1986) and when the absolute turnover rate was calculated the difference in the rate of glucose disposal between the physiologic and pharmacologic doses was 100-fold. Similar effects have been noted with the turnover of 1,25-dihydroxycholecalciferol before and after loading with the hormone (Frolik & DeLuca, 1973).…”

Section: Discussionsupporting

confidence: 80%

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

et al. 2002

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The aims of this study were to determine the total body phylloquinone and its metabolic turnover in human subjects using a tracer dose of [5-H 3 ]phylloquinone containing 55·5 £ 10 4 MBq=mmol. Seven subjects aged 22 to 49 years were given 0·3 mg isotopic phylloquinone intravenously on a control diet (75 mg phylloquinone/d) and blood, urine and faeces were sampled periodically for 6 d. Five of these subjects were studied a second time after 3 -8 weeks on a low-vitamin K diet (8 mg/d). The changes in the radioactivity of plasma phylloquinone with time were analysed by the method of residuals and fitted to a curve composed of two exponential components. The size of the exchangeable body pool was calculated by isotope dilution. Plasma phylloquinone levels fell during vitamin K restriction but the vitamin K-dependent coagulation factors did not change. After injection the first exponential decay curve t 1/2 was 1·0 (SD 0·47) h in the subjects on the control diet and 0·49 (SD 0·27) h after vitamin K restriction. On the control diet, the second exponential t 1/2 was 27·6 (SD 124) h that did not change on the low-vitamin K diet (t 1=2 ¼ 25·1 (SD 13·5) h). These results indicate that the turnover time for phylloquinone in human subjects is about 1·5 d. Urinary excretion of 3 H-metabolites ranged from 30 % of the administered dose on the control diet to 38 % on the restricted diet and had the same turnover rate as the second component of the plasma decay curves. The exchangeable body pool of phylloquinone declined from about 1·0 mg/kg before restriction to lower values after vitamin K restriction. The faecal excretion of phylloquinone and its metabolites fell from 32 % of the administered dose on the control diet to 13 % on the restricted diet. Vitamin K: Radioactive phylloquinone: Exchangeable body pool: Metabolic turnoverGreat advances have been made in the understanding of the distribution, function and metabolism of vitamin K since its discovery by Henrik Dam. (Dam, 1935;Olson, 1999) Less well documented is the content of vitamin K in the human body and the extent of its metabolic turnover. The first attempt to measure phylloquinone turnover in human subjects was made by Shearer et al. (1972), who administered 1 mg [1 0 , 2 0 -3 H 2 ]phylloquinone (200 MBq/ mmol) intravenously to each of three young male volunteers whose plasma was sampled at intervals for 96 h. They observed that after 2 h only 10 % of the initial radioactivity remained in the plasma space, and that the decay curves over 6 h could be resolved into two exponential functions with half-times of 20-24 min and 121-150 min. Later Shearer et al. (1974) repeated their study using 45 mg-phylloquinone of higher specific activity (3515 MBq/mmol) and obtained similar results. Bjornsson et al. (1979) carried out similar turnover studies in four healthy male volunteers using 300 mg [1 0 , 2 0 -3 H 2 ]phylloquinone (3237 MBq/mmol). They also observed two exponential components to the decay curves of 26 (SD 8) min and 166 (SD 10) min over 10 h.None of these invest...

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Section: Discussionsupporting

confidence: 80%

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

et al. 2002

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“…Comparing the responses to low dietary calcium at the age of [20][21][22][23][24] ing WKY, P < 0.005 (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

Abnormal vitamin D metabolism, intestinal calcium transport, and bone calcium status in the spontaneously hypertensive rat compared with its genetic control.

Lucas¹,

Brown²,

Drüeke³

et al. 1986

J. Clin. Invest.

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“…The stimulation of intestinal calcium and phosphorus transport both appear to be mediated by the 1,25-dihydroxy metabolite of vitamin D synthesized by the kidneys (11,12) from 25-hydroxycholecalciferol (25-OHD3)' which is derived from the hepatic hydroxylation of vitamin D3 (13). The earlier reported failure of orally administered 1,25-dihydroxycholecalciferol (1,25-(OH)2Da) to cure the rachitic state in rats (14) has now been attributed to the more rapid clearance of 1,25-(OH)2Ds relative to its immediate precursor, 25-OHD8 (15), which was effective in this regard. Accordingly, the 1,25-dihydroxy metabolite of cholecalciferol is considered to be the physiologically active form of the vitamin in mediating the mobilization of calcium and phosphorus from the intestine and bone.…”

Section: Introductionmentioning

confidence: 99%

25-hydroxycholecalciferol stimulation of muscle metabolism.

Birge¹,

Haddad²

1975

J. Clin. Invest.

240

111

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A B S T R A C T Intact diaphragms from vitamin D-deficient rats were incubated in vitro with ['H]leucine. Oral administration of 10 ug (400 U) of cholecalciferol 7 h before incubation increased leucine incorporation into diaphragm muscle protein by 136% (P <0.001) of the preparation from untreated animals. Nephrectomy did not obliterate this response. ATP content of the diaphragm muscle was also enhanced 7 h after administration of the vitamin. At 4 h after administration of cholecalciferol, serum phosphorus concentration was reduced by 0.7 mg/100 ml (P <0.025) and the rate of inorganic 'PO. accumulation by diaphragm muscle was increased by 18% (P < 0.025) over the untreated animals. Increasing serum phosphate concentration of the vitamin D-deficient animals by dietary supplementation with phosphate for 3 days failed to significantly enhance leucine incorporation into protein. However, supplementation of the rachitogenic, vitamin D-deficient diet with phosphorus for 3 wk stimulated the growth of the animal and muscle ATP levels. This increase in growth and muscle ATP content attributed to the addition of phosphorus to the diet was less than the increase in growth and muscle ATP levels achieved by the addition of both phosphorus and vitamin D to the diet.To eliminate systemic effects of the vitamin, the epitrochlear muscle of the rat foreleg of vitamin D-depleted rats was maintained in tissue culture. Addition of 20 ng/ml of Dr. Birge is a recipient of an American Heart Association Investigatorship. Dr. Haddad is a recipient of a National Institutes of Health Career Development Award.Received for publication 24 February 1975 and in revised form 9 July 1975. pg/ml were without effect. Analysis of muscle cytosol in sucrose density gradients revealed a protein fraction which specifically bound 25-OHD3 and which demonstrated a lesser affinity for 1,25-(OH)2D3. These studies suggest that 25-OHD3 may influence directly the intracellular accumulation of phosphate by muscle and thereby play an important role in the maintenance of muscle metabolism and function.

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The Stimulation of 1,25-Dihydroxycholecalciferol Metabolism in Vitamin D-deficient Rats by 1,25-Dihydroxycholecalciferol Treatment

Cited by 60 publications

References 26 publications

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

Abnormal vitamin D metabolism, intestinal calcium transport, and bone calcium status in the spontaneously hypertensive rat compared with its genetic control.

25-hydroxycholecalciferol stimulation of muscle metabolism.

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