Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake.
Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake.
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弧形胰高血糖素样肽1受体调节葡萄糖稳态，但不调节食物摄入量。
DOI：
10.2337/db07-1824
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发表时间：
2008-08
期刊：
影响因子：
7.7
通讯作者：
Seeley, Randy J.
中科院分区：
文献类型：
--
作者：
Sandoval, Darleen A.;Bagnol, Didier;Woods, Stephen C.;D'Alessio, David A.;Seeley, Randy J.
目的：胰高血糖素样肽-1 （glucagon -like peptide-1, GLP-1）通过调节胰岛激素分泌以及肝脏和胃功能来促进葡萄糖稳态。因为GLP-1也在大脑中合成，在那里它调节食物摄入，我们假设中枢GLP-1系统也调节葡萄糖耐量。研究设计和方法：我们使用糖耐量试验和高胰岛素-正糖钳来评估中枢GLP-1系统对糖耐量、胰岛素分泌、肝脏和外周胰岛素敏感性的作用。最后，采用原位杂交技术检测GLP-1受体与神经肽酪氨酸和前阿皮质素神经元的共定位。结果：我们发现，在葡萄糖耐量试验中，中枢而非外周给予低剂量GLP-1受体拮抗剂可引起相对高血糖，这表明中枢GLP-1受体的激活调节了参与维持葡萄糖稳态的关键过程。中央给药GLP-1增加了葡萄糖刺激的胰岛素分泌，直接给药GLP-1到下丘脑弓状核，而不是室旁核，减少了肝脏葡萄糖的产生。与GLP-1受体在弓形神经中的作用一致，GLP-1受体mRNA在68.1%的弓形神经细胞中表达，这些神经元表达前阿皮质素mRNA，但与神经肽酪氨酸不显著共表达。结论：这些数据表明弓形形GLP-1受体是GLP-1系统的关键组成部分，通过调节胰岛素分泌和葡萄糖产生来改善葡萄糖稳态。
OBJECTIVE—Glucagon-like peptide-1 (GLP-1) promotes glucose homeostasis through regulation of islet hormone secretion, as well as hepatic and gastric function. Because GLP-1 is also synthesized in the brain, where it regulates food intake, we hypothesized that the central GLP-1 system regulates glucose tolerance as well. RESEARCH DESIGN AND METHODS—We used glucose tolerance tests and hyperinsulinemic-euglycemic clamps to assess the role of the central GLP-1 system on glucose tolerance, insulin secretion, and hepatic and peripheral insulin sensitivity. Finally, in situ hybridization was used to examine colocalization of GLP-1 receptors with neuropeptide tyrosine and pro-opiomelanocortin neurons. RESULTS—We found that central, but not peripheral, administration of low doses of a GLP-1 receptor antagonist caused relative hyperglycemia during a glucose tolerance test, suggesting that activation of central GLP-1 receptors regulates key processes involved in the maintenance of glucose homeostasis. Central administration of GLP-1 augmented glucose-stimulated insulin secretion, and direct administration of GLP-1 into the arcuate, but not the paraventricular, nucleus of the hypothalamus reduced hepatic glucose production. Consistent with a role for GLP-1 receptors in the arcuate, GLP-1 receptor mRNA was found to be expressed in 68.1% of arcuate neurons that expressed pro-opiomelanocortin mRNA but was not significantly coexpressed with neuropeptide tyrosine. CONCLUSIONS—These data suggest that the arcuate GLP-1 receptors are a key component of the GLP-1 system for improving glucose homeostasis by regulating both insulin secretion and glucose production.
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影响因子：
4.8
作者：
MontroseRafizadeh, C;Yang, H;Eng, J
通讯作者：
Eng, J
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DRUCKER, DJ
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DRUCKER, DJ
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Chu, Zhi-Liang;Jones, Robert M.;Leonard, James
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Leonard, James
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Strader, CD
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作者：
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LUND, PK