Chang-Quan Huang, Bi-Rong Dong, Ping He, Zhen-Chan Lu
Geriatrics Department, West China Hospital of Sichuan University, Guoxuexiang 37, Chengdu, Sichuan, 610041, China.
J Bone Miner Metab. 2008;26(6):561-8. doi: 10.1007/s00774-008-0867-z. Epub 2008 Nov 1.
This study aimed to explore the relationship between insufficient renal 1-alpha hydroxylase (IRH) and bone homeostasis in type 2 diabetes mellitus (T2DM) or insulin resistance (IR) and to investigate whether IR plays a major role in the pathogenesis of both IRH and bone loss in T2DM. The experimental animal models of T2DM, IR, IR treated with vitamin D (VD), IR treated with 1-alpha hydroxyvitamin D (1alpha(OH) D, the product of renal 1-alpha hydroxylase), T2DM treated with VD, and T2DM treated with 1alpha(OH) D were established on 18-month-old male Wistar rats. For rats in each animal model and normal control rats, IR was detected by euglycemic insulin clamp technique (EICT) and glucose infusion rate (GIR, an index of IR) was calculated. Levels of serum 25-hydroxyvitamin D (25(OH)D) and serum active vitamin D (1,25(OH)(2)D) were determined by radioimmunoassay (RIA), and 1,25(OH)(2)D/25(OH)D ratio (1,25-25-R, an index of renal 1-alpha hydroxylase activity in vivo) was calculated; and bone mineral density (BMD) in femoral bone and lumbar vertebrae was measured by dual-energy X-ray absorption (DEXA). No significant difference was observed among the levels of 25(OH)D in all the rats. In IR rats, 1,25(OH)(2)D level, 1,25-25-R, and BMD level were significantly higher than those in T2DM rats and were lower than those in normal control rats. In the aged rats with T2DM or IR, administration of VD had no effect on 25(OH)D level, 1,25(OH)(2)D level, 1,25-25-R, and BMD level. Administration of 1alpha(OH) D had also no effect on 25(OH)D level but increased 1,25(OH)(2)D level, 1,25-25-R, and BMD level. For the aged rats with T2DM or IR, GIR positively correlated with both levels of 1,25(OH)(2)D and BMD, and 1,25-25-R positively and significantly correlated with levels of BMD. In T2DM or IR, IRH is a precipitating factor for bone loss. IR seems to play a major role in the pathogenesis of both IRH and bone loss in T2DM.
本研究旨在探讨2型糖尿病（T2DM）或胰岛素抵抗（IR）中肾脏1-α羟化酶不足（IRH）与骨稳态之间的关系，并研究IR在T2DM中IRH和骨质流失的发病机制中是否起主要作用。在18月龄雄性Wistar大鼠上建立了T2DM、IR、维生素D（VD）治疗的IR、1-α羟维生素D（1α(OH)D，肾脏1-α羟化酶的产物）治疗的IR、VD治疗的T2DM以及1α(OH)D治疗的T2DM的实验动物模型。对于每个动物模型中的大鼠和正常对照大鼠，采用正常血糖胰岛素钳夹技术（EICT）检测IR，并计算葡萄糖输注速率（GIR，IR的一个指标）。采用放射免疫分析法（RIA）测定血清25-羟维生素D（25(OH)D）和血清活性维生素D（1,25(OH)₂D）水平，并计算1,25(OH)₂D/25(OH)D比值（1,25-25-R，体内肾脏1-α羟化酶活性的一个指标）；采用双能X线吸收法（DEXA）测量股骨和腰椎的骨密度（BMD）。所有大鼠的25(OH)D水平之间未观察到显著差异。在IR大鼠中，1,25(OH)₂D水平、1,25-25-R和BMD水平显著高于T2DM大鼠，低于正常对照大鼠。在患有T2DM或IR的老年大鼠中，给予VD对25(OH)D水平、1,25(OH)₂D水平、1,25-25-R和BMD水平无影响。给予1α(OH)D对25(OH)D水平也无影响，但提高了1,25(OH)₂D水平、1,25-25-R和BMD水平。对于患有T2DM或IR的老年大鼠，GIR与1,25(OH)₂D水平和BMD均呈正相关，1,25-25-R与BMD水平呈显著正相关。在T2DM或IR中，IRH是骨质流失的一个促发因素。IR似乎在T2DM中IRH和骨质流失的发病机制中起主要作用。
