Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion
Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion
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DOI：
10.1007/s00125-006-0193-8
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发表时间：
2006-05-01
期刊：
影响因子：
8.2
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Tomita, T;Masuzuaki, H;Nakao, K
目的/假设G蛋白偶联受体40 （GPR40）在啮齿动物胰腺β细胞中大量表达，在体外促进葡萄糖诱导的胰岛素分泌，以响应中至长链脂肪酸。然而，GPR40基因在人类中的表达尚未得到充分的研究，对GPR40在人类中的生理和病理生理作用知之甚少。因此，本研究的目的是检测GPR40在人类中的表达及其临床意义。方法：采用TaqMan PCR方法分析人胰腺、胰岛及胰岛细胞肿瘤组织中mRNA的表达。结果：术中采集的人胰腺均检测到mRNA。它在从同一个体的胰腺新鲜制备的分离胰岛中富集约20倍。估计胰岛中GPR40基因的mRNA拷贝数与编码磺酰脲受体1、胰高血糖素样肽1受体和生长抑素受体的基因相当，所有这些基因都已知在人类胰岛中大量表达。在胰岛素瘤组织中检测到大量的GPR40 mRNA，而在胰高血糖素瘤和胃泌素瘤中未检测到mRNA的表达。胰腺中GPR40 mRNA水平与反映β细胞功能的胰岛素生成指数相关（r=0.82, p=0.044），但与OGTT期间的葡萄糖水平、OGTT曲线下的胰岛素面积或胰岛素抵抗的稳态模型评估指数（HOMA-IR）无关。结论/解释：本研究为GPR40基因在胰腺β细胞中的表达提供了证据，并提示GPR40与人类胰岛素分泌有关。
Aims/hypothesis G protein-coupled receptor 40 (GPR40) is abundantly expressed in pancreatic beta cells in rodents, where it facilitates glucose-induced insulin secretion in response to mid- to long-chain fatty acids in vitro. However, GPR40 gene expression in humans has not been fully investigated, and little is known about the physiological and pathophysiological roles of GPR40 in humans. The aim of this study, therefore, was to examine GPR40 expression and its clinical implications in humans.Methods :mRNA expression in the human pancreas, pancreatic islets and islet cell tumours was analysed using TaqMan PCR.Results: mRNA was detected in all human pancreases collected intraoperatively. It was enriched approximately 20-fold in isolated islets freshly prepared from the pancreases of the same individuals. The estimated mRNA copy number for the GPR40 gene in pancreatic islets was comparable to those for genes encoding sulfonylurea receptor 1, glucagon-like peptide 1 receptor and somatostatin receptors, all of which are known to be expressed abundantly in the human pancreatic islet. A large amount of GPR40 mRNA was detected in insulinoma tissues, whereas mRNA expression was undetectable in glucagonoma or gastrinoma. The GPR40 mRNA level in the pancreas correlated with the insulinogenic index, which reflects beta cell function (r=0.82, p=0.044), but not with glucose levels during the OGTT, the insulin area under the OGTT curve or the index for the homeostasis model assessment of insulin resistance (HOMA-IR).Conclusions/interpretation: The present study provides evidence for GPR40 gene expression in pancreatic beta cells and implicates GPR40 in insulin secretion in humans.