Ikeda K, Matsumoto T, Morita K, Yamato H, Takahashi H, Ezawa I, Ogata E
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Endocrinology. 1987 Nov;121(5):1721-6. doi: 10.1210/endo-121-5-1721.
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.
为评估胰岛素在甲状旁腺激素（PTH）刺激下1,25 - 二羟维生素D [1,25(OH)₂D]生成中的作用，分别在对照大鼠和链脲佐菌素诱导的糖尿病大鼠中，测定了饮食性钙（Ca）缺乏后以及PTH输注后肾匀浆中25 - 羟维生素D - 1α - 羟化酶活性和血清1,25(OH)₂D浓度。尽管饮食性钙缺乏1周后血清钙（Ca）和磷（Pi）水平无显著变化，但尿中环磷酸腺苷（cAMP）排泄显著增加，表明饮食性钙缺乏导致继发性甲状旁腺功能亢进，而血清钙水平无显著变化。在对照大鼠中，肾1α - 羟化酶活性从0.11±0.05显著增加至1.70±0.46 ng/300 mg组织/20分钟，同时血清1,25(OH)₂D水平从121±8 pg/ml变化至360±54 pg/ml，以响应钙缺乏。相反，正常钙饮食的糖尿病大鼠血清1,25(OH)₂D水平（82±3 pg/ml）和1α - 羟化酶活性（0.07±0.02 ng/300 mg组织·20分钟）低于对照大鼠，且糖尿病大鼠中钙缺乏后1,25(OH)₂D水平和1α - 羟化酶活性的增加受到抑制（钙缺乏后分别为136±24 pg/ml和0.38±0.12 ng/300 mg组织·20分钟）。对糖尿病大鼠进行胰岛素治疗可恢复血清1,25(OH)₂D（125±14 pg/ml）和肾1α - 羟化酶活性（0.21±0.02 ng/300 mg组织·20分钟）的基线水平以及钙缺乏后的水平（分别为340±52 pg/ml和2.05±0.30 ng/300 mg组织·20分钟）。此外，当对照大鼠和糖尿病大鼠进行甲状腺甲状旁腺切除并输注最大刺激剂量的PTH时，糖尿病大鼠中PTH刺激引起的血清1,25(OH)₂D和肾1α - 羟化酶活性增加受到显著抑制。另外，甲状腺甲状旁腺切除的糖尿病大鼠血清1,25(OH)₂D和肾1α - 羟化酶活性的基线水平与对照大鼠无差异。这些结果与以下结论一致，即胰岛素在响应PTH时对肾1α - 羟化酶活性和血清1,25(OH)₂D水平的调节中起重要作用。
