Verhaeghe J, Suiker A M, Van Bree R, Van Herck E, Jans I, Visser W J, Thomasset M, Allewaert K, Bouillon R
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit Leuven, Belgium.
Am J Physiol. 1993 Aug;265(2 Pt 1):E215-23. doi: 10.1152/ajpendo.1993.265.2.E215.
The kinetics of 1,25-dihydroxyvitamin D3 [1,25(OH)2-D3] and the in vivo response to 1,25(OH)2D3 (7.5, 15, and 30 ng/100 g body wt), infused or injected subcutaneously for 12-14 days, were studied in male spontaneously diabetic and control BB rats. In control rats, increasing doses of 1,25(OH)2D3 produced parallel increases in plasma 1,25(OH)2D3 and calcium, urinary calcium, duodenal CaBP9K, and renal CaBP28K. 1,25-(OH)2D3 at 30 ng/100 g markedly raised plasma osteocalcin and osteoblast/osteoid surfaces in the tibial metaphysis, but inhibited bone mineralization rate. In diabetic rats, plasma 1,25-(OH)2D3 concentrations were decreased, and the rise of plasma 1,25(OH)2D3 during 1,25(OH)2D3 infusion was blunted, but the free 1,25(OH)2D3 index remained normal or above normal. Diabetic rats had an increased metabolic clearance rate of 1,25-(OH)2D3 (0.38 +/- 0.015 vs. 0.24 +/- 0.007 ml.min-1.kg-1), with no further increase in 1,25(OH)2D3-infused diabetic rats; their relative production rate of 1,25(OH)2D3 was unchanged. The responses of plasma and urinary calcium, duodenal CaBP9K, and renal CaBP28K to infused 1,25(OH)2D3 were normal, as was duodenal calcium absorption in 1,25(OH)2D3-injected diabetic rats. However, the virtual absence of osteoblasts/osteoid in trabecular bone was unaltered in diabetic rats infused with 30 ng/100 g 1,25(OH)2D3, with only minimal increase of their low plasma osteocalcin levels. 1,25(OH)2D3 treatment therefore cannot be expected to reverse diabetic osteopenia.
研究了1,25 - 二羟基维生素D3[1,25(OH)2 - D3]的动力学以及皮下输注或注射1,25(OH)2D3（7.5、15和30 ng/100 g体重）12 - 14天对雄性自发性糖尿病BB大鼠和对照BB大鼠的体内反应。在对照大鼠中，1,25(OH)2D3剂量增加会使血浆1,25(OH)2D3、钙、尿钙、十二指肠CaBP9K和肾CaBP28K平行增加。30 ng/100 g的1,25 - (OH)2D3显著提高了血浆骨钙素以及胫骨近端干骺端的成骨细胞/类骨质表面，但抑制了骨矿化率。在糖尿病大鼠中，血浆1,25 - (OH)2D3浓度降低，输注1,25(OH)2D3期间血浆1,25(OH)2D3的升高变钝，但游离1,25(OH)2D3指数仍正常或高于正常。糖尿病大鼠的1,25 - (OH)2D3代谢清除率增加（0.38±0.015 vs. 0.24±0.007 ml·min-1·kg-1），输注1,25(OH)2D3的糖尿病大鼠未见进一步增加；其1,25(OH)2D3的相对生成率未改变。血浆和尿钙、十二指肠CaBP9K以及肾CaBP28K对输注1,25(OH)2D3的反应正常，注射1,25(OH)2D3的糖尿病大鼠十二指肠钙吸收也正常。然而，在输注30 ng/100 g 1,25(OH)2D3的糖尿病大鼠中，小梁骨中几乎没有成骨细胞/类骨质的情况未改变，其低血浆骨钙素水平仅略有增加。因此，不能期望1,25(OH)2D3治疗能逆转糖尿病性骨质减少。
