Retinoid X receptor expression in skeletal muscle of nondiabetic, obese and type 2 diabetic individuals

Abstract

Retinoid X receptor (RXR) is a nuclear receptor that functions as an obligate heterodimeric partner of peroxisome proliferator-activator receptor (PPAR). Studies have shown that the [alpha ] isoform of RXR and PPAR[gamma ] act synergistically to regulate gene expression and insulin action. The aim of the current study was to compare the expression and regulation of RXR in the primary insulin-sensitive tissue, skeletal muscle, of various degrees of insulin-resistant states including obese type 2 diabetic (T2D), obese nondiabetic (OND), and lean nondiabetic (LND) subjects. Insulin action/resistance was determined by a 3-hour hyperinsulinemic, euglycemic (5.0 to 5.5 mmol/L) clamp. Percutaneous biopsy of the vastus lateralis muscle was performed before and after the clamp. RXR[alpha ] mRNA was measured using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay, while protein was determined by Western blotting. All 3 isoforms of RXR, [alpha ], [beta ], and [gamma ], were present in skeletal muscle. Protein expression of RXR isoforms did not differ between groups; RXR [alpha ] mRNA was also similar between groups. Neither RXR [alpha ] mRNA, RXR -[beta ] nor -[gamma ] protein displayed significant relationships with any of the clinical or laboratory parameters measured, including insulin sensitivity. RXR [alpha ] exhibited a negative correlation with free fatty acids levels ( r, [minus ].42, P [lt ] .05). There was also no relationship between RXR [alpha ] and PPAR[gamma ] protein levels. RXR [alpha ] mRNA was unaltered following insulin infusion. We conclude that RXR isoform ([alpha ], [beta ], [gamma ]) expression is not tightly controlled by insulin, insulin resistance or type 2 diabetes. Instead, RXR isoforms are likely constitutive proteins or controlled by other factors.