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老年肥胖大鼠的胰岛素抵抗、肾损伤、肾1-α羟化酶与骨稳态

Insulin resistance, renal injury, renal 1-alpha hydroxylase, and bone homeostasis in aged obese rats.

作者信息

Chang-Quan Huang, Bi-Rong Dong, Ping He, Zhen-Chan Lu, Xiao-Dong Peng

机构信息

The West China Hospital of Sichuan University, Sichuan, China.

出版信息

Arch Med Res. 2008 May;39(4):380-7. doi: 10.1016/j.arcmed.2007.12.008. Epub 2008 Mar 4.

DOI:10.1016/j.arcmed.2007.12.008
PMID:18375248
Abstract

BACKGROUND

This study aimed to explore the relationship among insulin resistance (IR), renal injury, renal 1-alpha hydroxylase activity (RHA), and bone homeostasis in the presence of obesity.

METHODS

Obesity, obesity treated with vitamin D, and obesity treated with 1-alpha hydroxyvitamin D [1-alpha(OH)D] were studied in animal models using aged Wistar rats. Glucose infusion rates (GIR), levels of urinary albumin (UA), serum 25-hydroxyvitamin D [25-(OH)D], serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured.

RESULTS

GIR in obese rats decreased. A negative correlation existed between UA level and GIR in the aged obese rats, which did not exist in the normal control rats. Levels of serum 25(OH)D in all models were similar. Obese rats had lower levels of serum 1,25(OH)(2)D and BMD than normal control rats. Treating obese rats with vitamin D had no effect on levels of serum 25-(OH)D, serum 1,25(OH)(2)D, and BMD. Administration of 1alpha-(OH)D to obese rats significantly increased serum 1,25(OH)(2)D to above-normal levels and BMD to normal level. In obese rats, levels of serum 1,25(OH)(2)D and BMD in lumbar vertebrae and femoral bone were positively correlated with GIR, and the level of serum 1,25(OH)(2)D was negatively correlated with the UA level.

CONCLUSIONS

In the presence of obesity, IR, renal injury, decrease in RHA and bone loss exist. IR-injured kidney accounts for a decrease in RHA, which is a precipitating factor for bone loss.

摘要

背景

本研究旨在探讨肥胖情况下胰岛素抵抗(IR)、肾损伤、肾1-α羟化酶活性(RHA)和骨稳态之间的关系。

方法

使用老年Wistar大鼠在动物模型中研究肥胖、维生素D治疗的肥胖以及1-α羟基维生素D [1-α(OH)D]治疗的肥胖。测量葡萄糖输注率(GIR)、尿白蛋白(UA)水平、血清25-羟基维生素D [25-(OH)D]、血清1,25-二羟基维生素D [1,25(OH)(2)D]以及腰椎和股骨的骨密度(BMD)。

结果

肥胖大鼠的GIR降低。老年肥胖大鼠的UA水平与GIR之间存在负相关,而正常对照大鼠中不存在这种相关性。所有模型中的血清25(OH)D水平相似。肥胖大鼠的血清1,25(OH)(2)D水平和BMD低于正常对照大鼠。用维生素D治疗肥胖大鼠对血清25-(OH)D、血清1,25(OH)(2)D水平和BMD没有影响。给肥胖大鼠施用1α-(OH)D可使血清1,25(OH)(2)D显著升高至正常以上水平,并使BMD恢复至正常水平。在肥胖大鼠中,腰椎和股骨的血清1,25(OH)(2)D水平和BMD与GIR呈正相关,血清1,25(OH)(2)D水平与UA水平呈负相关。

结论

在肥胖情况下,存在IR、肾损伤、RHA降低和骨质流失。IR损伤的肾脏导致RHA降低,这是骨质流失的一个促发因素。

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