Hepatic glucose sensing via the CREB coactivator CRTC2 |
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| Authors: | Dentin Renaud Hedrick Susan Xie Jianxin Yates John Montminy Marc |
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| Institution: | Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. |
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| Abstract: | Chronic hyperglycemia contributes to the development of diabetes-associated complications. Increases in the concentration of circulating glucose activate the hexosamine biosynthetic pathway (HBP) and promote the O-glycosylation of proteins by O-glycosyl transferase (OGT). We show that OGT triggered hepatic gluconeogenesis through the O-glycosylation of the transducer of regulated cyclic adenosine monophosphate response element-binding protein (CREB) 2 (TORC2 or CRTC2). CRTC2 was O-glycosylated at sites that normally sequester CRTC2 in the cytoplasm through a phosphorylation-dependent mechanism. Decreasing amounts of O-glycosylated CRTC2 by expression of the deglycosylating enzyme O-GlcNAcase blocked effects of glucose on gluconeogenesis, demonstrating the importance of the HBP in the development of glucose intolerance. |
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