Yin Yang 1 Promotes Hepatic Gluconeogenesis Through Upregulation of Glucocorticoid Receptor
- Yan Lu1,
- Xuelian Xiong1,
- Xiaolin Wang1,
- Zhijian Zhang1,
- Jin Li1,
- Guojun Shi1,
- Jian Yang1,
- Huijie Zhang1,
- Guang Ning1,2⇑ and
- Xiaoying Li1,2,3⇑
- 1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2Key Laboratory of Endocrine Tumors and the Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai, China
- 3Chinese-French Laboratory of Genomics and Life Sciences, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Corresponding author: Guang Ning, , or Xiaoying Li, .
Y.L. and X.X. equally contributed to this work.
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0744/-/DC1.
- Received June 12, 2012.
- Accepted October 6, 2012.
- © 2013 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.