Does chasing selected 'Fox' to the nucleus prevent diabetes?
Foxa2 (Hnf3beta) is a winged-helix/forkhead transcription factor that regulates gene expression in the liver, pancreatic islets and adipocytes. It is required for the maintenance of glucose and lipid homeostasis. Hyperinsulinemia-mediated inactivation of Foxa2 by nuclear exclusion has recently been implicated in the development of liver steatosis and insulin resistance in three animal models of diabetes. These abnormalities were cured by adenovirus-mediated expression of a constitutively active form of Foxa2 containing a mutated T156 phosphorylation site, which increases fatty acid oxidation and reduces its biosynthesis. Accordingly, the prevention of phosphorylation of Foxa2 was suggested as a pharmacological target for the treatment of obesity and diabetes.
Wang
Haiyan
H
Department of Cell Physiology and Metabolism, University Medical Center, CH-1211 Geneva 4, Switzerland. Haiyan.Wang@medicine.unige.ch
Wollheim
Claes B
CB
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000517:prevention & control; D005227:Fatty Acids / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta; D006706:Homeostasis; D006801:Humans; D007003:Hypoglycemia; D007333:Insulin Resistance; D007515:Islets of Langerhans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; C085126:FOXO1 protein, human; D005227:Fatty Acids; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D005947:Glucose; D010100:Oxygen