NR4A1 (also known as Nur77, TR3) is an orphan nuclear receptor first identified as an immediate early response gene (transient serum induction). NR4A1 dimerizes with RXR and synergizes in a retinoid-dependent manner. Phosphorylation of NR4A1 may regulate subcellular localization of RXR, which also binds PPAR. NR4A1 may translocate from nucleus to the outer mitochondrial membrane and regulate apoptosis (proapoptotic). In Mexican-Americans, Dr. Patti identified NR4A1 as a gene differentially expressed in insulin resistant and diabetic subjects. xpression is significantly increased in insulin resistant nondiabetic subjects (family history positive) as compared with nondiabetic subjects without a family history of diabetes, as well as in diabetic individuals. NR4A1 expression is also reduced by clinical treatment with the insulin sensitizer and PPAR ligand rosiglitazone in both humans with type 2 diabetes and in control mice, suggesting a potential role for changes in NR4A1 to mediate metabolic improvements with TZD.

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