Abstract |
A nonsense mutation in cereblon (CRBN) causes a mild type of mental retardation in humans. An earlier study showed that CRBN negatively regulates the functional activity of AMP-activated protein kinase (AMPK) in vitro by binding directly to the α1-subunit of the AMPK complex. However, the in vivo role of CRBN was not studied. For elucidation of the physiological functions of Crbn, a mouse strain was generated in which the Crbn gene was deleted throughout the whole body. In Crbn-deficient mice fed a normal diet, AMPK in the liver showed hyperphosphorylation, which indicated the constitutive activation of AMPK. Since Crbn-deficient mice showed significantly less weight gain when fed a high-fat diet and their insulin sensitivity was considerably improved, the functions of Crbn in the liver were primarily investigated. These results provide the first in vivo evidence that Crbn is a negative modulator of AMPK, which suggests that Crbn may be a potential target for metabolic disorders of the liver.
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Authors | Kwang Min Lee, Seung-Joo Yang, Yong Deuk Kim, Yoo Duk Choi, Jong Hee Nam, Cheol Soo Choi, Hueng-Sik Choi, Chul-Seung Park |
Journal | Diabetes
(Diabetes)
Vol. 62
Issue 6
Pg. 1855-64
(Jun 2013)
ISSN: 1939-327X [Electronic] United States |
PMID | 23349485
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- CRBN protein, human
- Ubiquitin-Protein Ligases
- AMP-Activated Protein Kinases
- Peptide Hydrolases
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Topics |
- AMP-Activated Protein Kinases
(metabolism)
- Adaptor Proteins, Signal Transducing
- Animals
- Diet, High-Fat
(adverse effects)
- Female
- Insulin Resistance
(genetics, physiology)
- Liver
(enzymology)
- Male
- Mice
- Mice, Knockout
- Obesity
(etiology, genetics, therapy)
- Peptide Hydrolases
(genetics, metabolism)
- Ubiquitin-Protein Ligases
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