Inada A, Yamada Y, Someya Y, Kubota A, Yasuda K, Ihara Y, Kagimoto S, Kuroe A, Tsuda K, Seino Y
Department of Metabolism and Clinical Nutrition, Faculty of Medicine, Kyoto University, Japan.
Biochem Biophys Res Commun. 1998 Dec 30;253(3):712-8. doi: 10.1006/bbrc.1998.9833.
To further clarify the mechanism of impaired insulin gene transcription in the diabetic state, we investigated the expression and function of the transcriptional repressor CREM (CRE modulator) in rat pancreatic islets. The CREM gene generates both transcriptional activators and repressors by alternative splicing and an intronic promoter. We isolated a novel alternatively spliced CREM isoform, CREM-17X, which efficiently represses insulin gene transcription, in addition to the three previously reported repressors. We also compared mRNA levels of insulin and the CREM repressors in pancreatic islets of Wistar and GK (Goto-Kakizaki) rats, the well-characterized spontaneous animal model of type 2 diabetes. The CREM repressor levels are increased, and the expression of insulin mRNA is decreased in GK rats, suggesting that increased CREM repressor expression in pancreatic islets could contribute to the decreased insulin gene transcription that results in impaired insulin secretion in type 2 diabetes.
为进一步阐明糖尿病状态下胰岛素基因转录受损的机制，我们研究了转录抑制因子CREM（CRE调节因子）在大鼠胰岛中的表达及功能。CREM基因通过可变剪接和一个内含子启动子产生转录激活因子和抑制因子。我们分离出一种新的可变剪接的CREM亚型，即CREM-17X，除了之前报道的三种抑制因子外，它还能有效抑制胰岛素基因转录。我们还比较了Wistar大鼠和GK（Goto-Kakizaki）大鼠胰岛中胰岛素和CREM抑制因子的mRNA水平，GK大鼠是一种特征明确的2型糖尿病自发性动物模型。GK大鼠中CREM抑制因子水平升高，胰岛素mRNA表达降低，这表明胰岛中CREM抑制因子表达增加可能导致胰岛素基因转录减少，进而导致2型糖尿病患者胰岛素分泌受损。
