Circadian regulation of islet genes involved in insulin production and secretion
Circadian regulation of islet genes involved in insulin production and secretion
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DOI：
10.1016/j.mce.2004.06.001
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发表时间：
2004-10-29
影响因子：
4.1
通讯作者：
Bonny, C
中科院分区：
文献类型：
--
作者：
Allaman-Pillet, N;Roduit, R;Bonny, C
转录因子白蛋白位点D结合蛋白（DBP）和促甲状腺细胞胚胎因子（TEF）都是“细胞时钟”的组成部分。它们在视交叉上核（SCN）和外周组织如肝、肾和肺中的昼夜累积被认为参与控制下游基因的昼夜调节。胰岛素分泌细胞中的TEF和DBP调控元件从未被研究过，但β细胞的昼夜节律受损可能参与了糖尿病状态的发展，因为2型糖尿病患者失去了胰岛素分泌的每日时间变化。与其他组织相比，TEF和DBP转录本在人类胰岛中的表达水平极高，这表明这些细胞的昼夜节律调节可能很重要。TEF和DPB在血清休克后以昼夜节律的方式在胰岛素分泌细胞中积累，已知血清休克可恢复培养细胞中的昼夜节律。此外，参与葡萄糖传感（葡萄糖转运蛋白2（Glut2），葡萄糖激酶），胰岛素产生（胰岛素）和分泌（迁移抑制因子（MIF），生长抑素和syntaxin 1A）的胰岛特异性基因的表达也在相同的每日节律中调节。因此，这些基因的昼夜节律失调可能参与糖尿病状态的发展。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Both transcription factors albumin site D-binding protein (DBP) and thyrotroph embryonic factor (TEF) are elements of the "cell-clock". Their circadian accumulation in suprachiasmatic nucleus (SCN) and peripheral tissues such as liver, kidney and lung is thought to participate in controlling circadian regulation of downstream genes. TEF and DBP control elements have never been investigated in the insulin-secreting cells, but impairment of the circadian rhythm of the beta-cells might be involved in the development of diabetic state as type 2 diabetics have lost daily temporal variations of insulin secretion.We investigated the expression pattern of TEF and DBP in insulin-secreting cells. TEF and DBP transcripts are expressed at extremely high levels in human pancreatic islets compared to other tissues, suggesting a potentially important circadian regulation of these cells. Both TEF and DPB accumulate in a circadian way in insulin-secreting cells after a serum shock known to restore circadian rhythms in cultured cells. In addition, the expression of islet-specific genes involved in glucose sensing (glucose transporter 2 (Glut2), glucokinase), insulin production (insulin) and secretion (migration inhibitory factor (MIF), somatostatin and syntaxin 1A) were modulated in the same daily rhythm as well. The circadian deregulation of these genes could therefore participate in the diabetic state development. (C) 2004 Elsevier Ireland Ltd. All rights reserved.