Adiponectin is an adipose-derived hormone that has anti-diabetic and anti-atherogenic effects through interaction with adiponectin receptors AdipoR1 and AdipoR2. We analyzed the transcriptional regulation of AdipoR1 by insulin. Insulin repressed the promoter activity of AdipoR1 in C2C12 myoblasts via PI3K and Foxo1. Deletion studies demonstrated the presence of a putative insulin-responsive region which is composed of a nuclear inhibitory protein (NIP) binding element. Mutation of the NIP element abrogated the negative regulation of AdipoR1 promoter by insulin. Insulin treatment could induce formation of a protein complex that bound the NIP element. Collectively, our data suggest that a repressive NIP element is involved in the negative regulation of AdipoR1 promoter by insulin.
Bibliographical noteFunding Information:
We wish to thank Dr. K.L. Guan and Dr. Eric D. Tang from Institute of Gerontology, University of Michigan Medical School Ann Arbor, USA, for providing the plasmids. This work was supported by research grants from Chinese Academy of Sciences (One Hundred Talents Program and the Knowledge Innovation Program KSCX1-YW-02), National Natural Science Foundation of China (30588002 and 30470870), and the Ministry of Science and Technology of China (2007CB947100 and 2007CB947100) to Y.C.
- Adiponectin receptor
- Nuclear inhibitory protein element