deregulation of creb signaling pathway induced by chronic hyperglycemia downregulates neurod transcription放松管制的分子信号通路引起的慢性高血糖会使neurod转录.pdfVIP

Deregulation of CREB Signaling Pathway Induced by Chronic Hyperglycemia Downregulates NeuroD Transcription 1,3,4 2 7 2 8 9 In-Su Cho , Miyoung Jung , Ki-Sun Kwon , Eunpyo Moon , Jang-Hyeon Cho , Kun-Ho Yoon , Ji- Won Kim9, Young-Don Lee1,5,6, Sung-Soo Kim 1,6*, Haeyoung Suh-Kim1,3,4* 1 Department of Anatomy, Ajou University, Suwon, South Korea, 2 Department of Biological Sciences, Ajou University, Suwon, South Korea, 3 Graduate Neuroscience Program, Ajou University, Suwon, South Korea, 4 BK21, Division of Cell Transformation and Restoration, Ajou University, Suwon, South Korea, 5 Molecular Science and Technology, Ajou University, Suwon, South Korea, 6 Control for Cell Death Regulating Biodrug, Ajou University, Suwon, South Korea, 7 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea, 8 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America, 9 Department of Endocrinology, Catholic University, School of Medicine, Seoul, South Korea Abstract CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing b- cells. Although the inhibition of CREB activity is known to decrease the b-cell mass, it is still unknown what factors inversely alter the CREB signaling pathway in b-cells. Here, we show that b-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A. When freshly isolated rat pancreatic islets were chronically exposed to 25 mM (high) glucose, the PP2A activity was reduced with a concomitant increase in active pCREB. Brief challenges with 15 mM glucose