Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice
National Institutes of Health · Research Triangle Park Foundation · +3 more institutions
Abstract
Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In…
Citation impact
- FWCI
- 17.78
- Percentile
- 100%
- References
- 52
Authors
8- YZYanqiao ZhangCorresponding
National Institutes of Health, Research Triangle Park Foundation, University of California, Los Angeles, GlaxoSmithKline (United States), National Cancer Institute
- FYFlorence Ying Lee
National Institutes of Health, Research Triangle Park Foundation, University of California, Los Angeles, GlaxoSmithKline (United States), National Cancer Institute
- GBGabriel Barrera
National Institutes of Health, Research Triangle Park Foundation, University of California, Los Angeles, GlaxoSmithKline (United States), National Cancer Institute
- HCHans C. Lee
National Institutes of Health, Research Triangle Park Foundation, University of California, Los Angeles, GlaxoSmithKline (United States), National Cancer Institute
- CVCharisse Vales
National Institutes of Health, Research Triangle Park Foundation, University of California, Los Angeles, GlaxoSmithKline (United States), National Cancer Institute
Topics & keywords
- Farnesoid X receptor
- Internal medicine
- Endocrinology
- Nuclear receptor
- Glucose homeostasis
- Agonist
- Carbohydrate metabolism
- Glycogen
- Good health and well-being