氨基葡萄糖诱导去卵巢大鼠胰岛素抵抗与骨骼肌葡萄糖转运蛋白亚型 4 表达减少和胰岛增大有关。

Glucosamine-induced insulin resistance in ovariectomized rats is relevant to decreasing the expression of glucose transport protein subtype 4 in the skeletal muscle and in increasing the size of pancreatic islets.

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.

出版信息

Menopause. 2012 May;19(5):496-502. doi: 10.1097/gme.0b013e31823a40d9.

DOI:10.1097/gme.0b013e31823a40d9

PMID:22240637

Abstract

OBJECTIVE

Glucosamine (GlcN) is a popular nutritional supplement used to treat osteoarthritis in postmenopausal women. Postmenopausal women are at higher risk of type 2 diabetes mellitus and metabolic syndrome because of ovarian hormone deficiency. We used ovariectomized (OVX) rats as the model to investigate whether GlcN would induce insulin resistance (IR) in OVX rats and the underlying mechanisms.

METHODS

The rats were divided into four groups: (1) sham-operated group (SHAM), (2) SHAM with GlcN treatment (SHAM + GlcN), (3) OVX group, (4) OVX with GlcN treatment (OVX + GlcN). Intraperitoneal (IP) GlcN was given at 12 weeks after the surgical procedure for 2 weeks. The IP glucose tolerance test (IPGTT) was performed to measure plasma glucose and insulin and to calculate the clinical homeostasis model assessment-IR (HOMA-IR) and glucose-insulin index. Western blot analysis for the detection of glucose transport protein subtype 4 expression in the skeletal muscle and histopathological examination of the changes in pancreatic islets were also performed.

RESULTS

Fasting plasma glucose increased in the OVX + GlcN group, and fasting plasma insulin and HOMA-IR were elevated more significantly in this group. In addition, plasma glucose, plasma insulin, HOMA-IR, and glucose-insulin index were significantly elevated only in the OVX with GlcN group after IP glucose injection, implying that IR was induced by GlcN only in female rats without the protection of ovarian hormone. In addition, we found that treatment with GlcN decreased the expression of glucose transport protein subtype 4 in the skeletal muscle and induced pancreatic islet hyperplasia only in OVX rats.

CONCLUSIONS

The results demonstrate that female rats do not develop IR upon GlcN treatment except after ovariectomy. Those who take GlcN after menopause or bilateral oophorectomy should watch their blood glucose level closely, especially after meals.

摘要

目的

氨基葡萄糖（GlcN）是一种常用于治疗绝经后女性骨关节炎的流行营养补充剂。由于卵巢激素缺乏，绝经后女性患 2 型糖尿病和代谢综合征的风险更高。我们使用去卵巢（OVX）大鼠作为模型，研究 GlcN 是否会在 OVX 大鼠中引起胰岛素抵抗（IR）及其潜在机制。

方法

大鼠分为四组：（1）假手术组（SHAM），（2）SHAM 加 GlcN 治疗组（SHAM+GlcN），（3）OVX 组，（4）OVX 加 GlcN 治疗组（OVX+GlcN）。手术后 12 周开始给予腹腔内（IP）GlcN 治疗 2 周。进行 IP 葡萄糖耐量试验（IPGTT）以测量血浆葡萄糖和胰岛素，并计算临床稳态模型评估-IR（HOMA-IR）和葡萄糖-胰岛素指数。还进行了骨骼肌葡萄糖转运蛋白亚型 4 表达的 Western blot 分析和胰腺胰岛组织学检查。

结果

OVX+GlcN 组大鼠空腹血糖升高，该组大鼠空腹胰岛素和 HOMA-IR 升高更为显著。此外，仅在 OVX 加 GlcN 组大鼠 IP 葡萄糖注射后，血浆葡萄糖、血浆胰岛素、HOMA-IR 和葡萄糖-胰岛素指数显著升高，表明 GlcN 仅在无卵巢激素保护的雌性大鼠中引起 IR。此外，我们发现 GlcN 治疗降低了骨骼肌中葡萄糖转运蛋白亚型 4 的表达，仅在 OVX 大鼠中引起胰岛增生。