The role of insulin in the stimulation of renal 1,25-dihydroxyvitamin D synthesis by parathyroid hormone in rats.
To evaluate the role of insulin in 1,25-dihydroxyvitamin D [1,25(OH)2D] production in response to PTH, 25-hydroxyvitamin D-1 alpha-hydroxylase activity in kidney homogenates as well as serum 1,25(OH)2D concentration was measured both after dietary calcium (Ca) deprivation and after PTH infusion in control and streptozotocin-diabetic rats. Although serum Ca and phosphate (Pi) levels did not change significantly after dietary Ca deprivation for 1 week, urinary cAMP excretion increased significantly, indicating that dietary Ca deprivation caused secondary hyperparathyroidism without a significant change in serum Ca level. In control rats, renal 1 alpha-hydroxylase activity increased markedly from 0.11 +/- 0.05 to 1.70 +/- 0.46 ng/300 mg tissue/20 min in parallel with the change in serum 1,25(OH)2D level from 121 +/- 8 to 360 +/- 54 pg/ml in response to Ca deprivation. In contrast, serum 1,25(OH)2D level (82 +/- 3 pg/ml) and 1 alpha-hydroxylase activity (0.07 +/- 0.02 ng/300 mg tissue.20 min) were lower in the diabetic rats on a normal Ca diet than those in control rats, and the increase in both 1,25(OH)2D level and 1 alpha-hydroxylase activity in response to Ca deprivation was suppressed in diabetic rats (136 +/- 24 pg/ml and 0.38 +/- 0.12 ng/300 mg tissue.20 min, respectively, after Ca deprivation). Insulin treatment of the diabetic rats restored the baseline levels of serum 1,25(OH)2D (125 +/- 14 pg/ml) and renal 1 alpha-hydroxylase activity (0.21 +/- 0.02 ng/300 mg tissue.20 min) as well as those after Ca deprivation (340 +/- 52 pg/ml and 2.05 +/- 0.30 ng/300 mg tissue.20 min, respectively). Furthermore, when control and diabetic rats were thyroparathyroidectomized and infused with a maximal stimulatory dose of PTH, the increase in serum 1,25(OH)2D and renal 1 alpha-hydroxylase activity in response to PTH was markedly inhibited in diabetic rats. In addition, the baseline levels of serum 1,25(OH)2D and renal 1 alpha-hydroxylase activity in thyroparathyroidectomized diabetic rats were not different from those in control rats. These results are consistent with the conclusion that insulin plays an important role in the regulation of renal 1 alpha-hydroxylase activity and serum 1,25(OH)2D levels in response to PTH.
Ikeda
K
K
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Matsumoto
T
T
Morita
K
K
Yamato
H
H
Takahashi
H
H
Ezawa
I
I
Ogata
E
E
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002117:Calcitriol / Q000096:biosynthesis* / Q000097:blood; D002118:Calcium / Q000097:blood / Q000172:deficiency; D002136:Calcium, Dietary / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D006961:Hyperparathyroidism / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D013250:Steroid Hydroxylases / Q000378:metabolism*
D002136:Calcium, Dietary; D007328:Insulin; D010281:Parathyroid Hormone; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002118:Calcium