Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas
Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas
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DOI：
10.1677/joe-10-0044
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发表时间：
2010-10-01
影响因子：
4
通讯作者：
Jin, Tianru
中科院分区：
文献类型：
--
作者：
Columbus, Joshua;Chiang, YuTing;Jin, Tianru
人类 TCF7L2 内含子区域的特定单核苷酸多态性与患 2 型糖尿病的风险升高相关。然而，Tcf7l2 在啮齿类动物的胰岛中是否以相当水平表达仍存在争议。我们使用 RT-PCR 和定量 RT-PCR 来检测啮齿动物肠道、胰腺、分离胰岛和培养细胞系中的 Tcf7l2 表达。与肠道或胰腺 β 细胞系 Ins-1 相比，胰腺中 Tcf7l2 的表达水平相对较低。免疫染色未在小鼠胰岛中检测到 Tcf7l2 信号。 TOPGAL 转基因小鼠的胰腺内源性经典 Wnt 活性并不明显。 Tcf7 和 Tcf7l1 均在胰腺中表达，但 Lef1 不表达。胰岛素治疗或高脂饮食喂养会降低胰腺中三种 Tcf 基因（Tcf7、Tcf7l1 和 Tcf7l2）的表达，而胰岛素会刺激肠道中的 Tcf7l2 表达。我们认为高胰岛素血症会抑制胰腺中 Tcf 基因的表达。这种减少是否以及如何改变高胰岛素血症期间胰腺β细胞的功能值得进一步研究。内分泌学杂志 (2010) 207, 77-86
Specific single-nucleotide polymorphisms in intronic regions of human TCF7L2 are associated with an elevated risk of developing type 2 diabetes. Whether Tcf7l2 is expressed in pancreatic islets of rodent species at a considerable level, however, remains controversial. We used RT-PCR and quantitative RT-PCR to examine Tcf7l2 expression in rodent gut, pancreas, isolated pancreatic islets, and cultured cell lines. The expression level of Tcf7l2 was relatively lower in the pancreas compared to the gut or the pancreatic beta-cell line Ins-1. Immunostaining did not detect a Tcf7l2 signal in mouse pancreatic islets. Endogenous canonical Wnt activity was not appreciable in the pancreas of TOPGAL transgenic mice. Both Tcf7 and Tcf7l1, but not Lef1, were expressed in the pancreas. The expression of the three Tcf genes (Tcf7, Tcf7l1, and Tcf7l2) in the pancreas was reduced by treatment with insulin or high-fat diet feeding, in contrast to the stimulation of Tcf7l2 expression by insulin in the gut. We suggest that hyperinsulinemia represses Tcf gene expression in the pancreas. Whether and how this reduction alters the function of pancreatic beta cells during hyperinsulinemia deserves further investigation. Journal of Endocrinology (2010) 207, 77-86