Yin Yang 1 promotes hepatic gluconeogenesis through upregulation of glucocorticoid receptor.

Abstract	Gluconeogenesis is critical in maintaining blood glucose levels in a normal range during fasting. In this study, we investigated the role of Yin Yang 1 (YY1), a key transcription factor involved in cell proliferation and differentiation, in the regulation of hepatic gluconeogenesis. Our data showed that hepatic YY1 expression levels were induced in mice during fasting conditions and in a state of insulin resistance. Overexpression of YY1 in livers augmented gluconeogenesis, raising fasting blood glucose levels in C57BL/6 mice, whereas liver-specific ablation of YY1 using adenoviral shRNA ameliorated hyperglycemia in wild-type and diabetic db/db mice. At the molecular level, we further demonstrated that the major mechanism of YY1 in the regulation of hepatic glucose production is to modulate the expression of glucocorticoid receptor. Therefore, our study uncovered for the first time that YY1 participates in the regulation of hepatic gluconeogenesis, which implies that YY1 might serve as a potential therapeutic target for hyperglycemia in diabetes.
Authors	Yan Lu, Xuelian Xiong, Xiaolin Wang, Zhijian Zhang, Jin Li, Guojun Shi, Jian Yang, Huijie Zhang, Guang Ning, Xiaoying Li
Journal	Diabetes (Diabetes) Vol. 62 Issue 4 Pg. 1064-73 (Apr 2013) ISSN: 1939-327X [Electronic] United States
PMID	23193188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Blood Glucose Cyclic AMP Response Element-Binding Protein Receptors, Glucocorticoid YY1 Transcription Factor Yy1 protein, mouse Cyclic AMP Ncoa1 protein, mouse Nuclear Receptor Coactivator 1
Topics	Animals Blood Glucose Cell Line Cyclic AMP (genetics, metabolism) Cyclic AMP Response Element-Binding Protein (genetics, metabolism) Food Deprivation Gene Expression Regulation (physiology) Gluconeogenesis (physiology) Humans Hyperglycemia (metabolism) Insulin Resistance Liver (metabolism) Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, Transgenic Nuclear Receptor Coactivator 1 (genetics, metabolism) Receptors, Glucocorticoid (genetics, metabolism) Signal Transduction Up-Regulation YY1 Transcription Factor (genetics, metabolism)

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