Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats
Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats
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DOI：
10.1530/eje.1.02046
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发表时间：
2005-12-01
影响因子：
5.8
通讯作者：
Brand, CL
中科院分区：
文献类型：
--
作者：
Gram, DX;Hansen, AJ;Brand, CL
目的：辣椒素诱导的脱敏可改善正常大鼠的胰岛素敏感性。然而，在饮食引起的肥胖中，辣椒素敏感神经活动的增加是否先于胰岛素抵抗的发生——因此可能与病理生理学有关——尚不清楚。此外，研究辣椒素脱敏是否能改善肥胖个体的血糖控制也是相关的，因此我们选择了肥胖的Zucker大鼠来测试这一点。设计和方法：测定8周龄Zucker大鼠血浆降钙素基因相关肽（CGRP，感觉神经活动的标志物）水平。为了研究辣椒素脱敏（9周龄时100 mg/kg）是否也会改善非糖尿病模型的血糖，我们在服用辣椒素后7周评估了口服葡萄糖耐量。结果：肥胖Zucker大鼠在肥胖前血浆CGRP水平升高（肥胖前Zucker大鼠为16.1 +/- 3.4 pmol/l，而瘦仔鼠为6.9 +/- 1.1 pmol/l, P = 0.015），尽管体重相似。此外，辣椒素脱敏降低了空腹血糖（对照组为4.3 +/- 0.2 mmol/l，对照组为5.1 +/- 0.2 mmol/l, P = 0.050）和口服葡萄糖耐量试验（OGTT）期间的平均血糖水平（对照组为6.8 +/- 0.3 mmol/l，对照组为8.6 +/- 0.5 mmol/l, P = 0.024），而OGTT期间的血浆胰岛素水平不变。然而，这并没有导致胰岛素抵抗的改善或肌肉或肝脏组织甘油三酯积累的减少。结论：辣椒素诱导的感觉神经脱敏可改善Zucker大鼠的葡萄糖耐量。由于在本研究中，血浆CGRP水平（感觉神经活动的标志）在肥胖前的大鼠中增加，我们的数据支持了感觉神经活动增加先于Zucker大鼠肥胖和胰岛素抵抗发展的假设。
Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity - and therefore might be involved in the pathophysiology - is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this.Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin.Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1 +/- 3.4 pmol/l in pre-obese Zucker rats vs 6.9 +/- 1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3 +/- 0.2 mmol/l vs 5.1 +/- 0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8 +/- 0.3 mmol/l vs 8.6 +/- 0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver.Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.