Nuclear hormone receptor expression in the endocrine pancreas
Nuclear hormone receptor expression in the endocrine pancreas
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DOI：
10.1210/me.2007-0568
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发表时间：
2008-10-01
影响因子：
--
通讯作者：
Repa, Joyce J.
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文献类型：
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作者：
Chuang, Jen-Chieh;Cha, Ji-Young;Repa, Joyce J.
内分泌胰腺由朗格汉斯胰岛组成，朗格汉斯胰岛是一小群细胞，仅占胰腺总质量的2%。然而，这个微小的内分泌器官通过调节胰岛素(由β细胞)和胰升血糖素(由α细胞)的分泌，在维持葡萄糖动态平衡方面发挥着关键作用。世界范围内糖尿病发病率的快速增长重新激发了人们对胰岛细胞生物学的兴趣。一些最广泛用于治疗2型糖尿病的口服药物包括结合和激活核激素受体的药物，即过氧化物酶体增殖物激活受体-伽马。作为解决过氧化物酶体增殖物激活受体-伽马和其他核激素受体(NHR)在胰腺内分泌生物学中的潜在作用的第一步，我们使用实时定量聚合酶链式反应(QRT-PCR)分析了小鼠NHR超家族的所有49个成员在初级胰岛以及代表α细胞(αTC1)和β细胞(βTC6和MIN6)的细胞系中的表达。综上所述，19个NHR成员在α和β细胞系中均高表达，13个受体在α和β细胞系中优势表达(至少差异8倍)。10个NHR在内分泌胰腺中不表达。此外，我们评估了这些转录因子在高血糖期间的相对表达，发现16个NHR在小鼠胰岛中的mRNA水平发生了显着变化。在原代人类胰岛中进行了类似的调查，发现了小鼠和人在NHR表达上的几个显著差异。这些数据确定了内分泌胰腺治疗糖尿病的潜在治疗靶点。
The endocrine pancreas comprises the islets of Langerhans, tiny clusters of cells that contribute only about 2% to the total pancreas mass. However, this little endocrine organ plays a critical role in maintaining glucose homeostasis by the regulated secretion of insulin (by beta- cells) and glucagon (by alpha- cells). The rapid increase in the incidence of diabetes worldwide has spurred renewed interest in islet cell biology. Some of the most widely prescribed oral drugs for treating type 2 diabetes include agents that bind and activate the nuclear hormone receptor, peroxisome proliferator- activated receptor-gamma. As a first step in addressing potential roles of peroxisome proliferator-activated receptor-gamma and other nuclear hormone receptors (NHRs) in the biology of the endocrine pancreas, we have used quantitative real- time PCR to profile the expression of all 49 members of the mouse NHR superfamily in primary islets, and cell lines that represent alpha-cells (alpha TC1) and beta-cells (beta TC6 and MIN6). In summary, 19 NHR members were highly expressed in both alpha-and beta-cell lines, 13 receptors showed predominant expression (at least an 8-fold difference) in alpha-vs. beta-cell lines, and 10 NHRs were not expressed in the endocrine pancreas. In addition we evaluated the relative expression of these transcription factors during hyperglycemia and found that 16 NHRs showed significantly altered mRNA levels in mouse islets. A similar survey was conducted in primary human islets to reveal several significant differences in NHR expression between mouse and man. These data identify potential therapeutic targets in the endocrine pancreas for the treatment of diabetes mellitus.