Retinoid X receptor expression in skeletal muscle of nondiabetic, obese and type 2 diabetic individuals.
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 PPARgamma 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. RXRalpha 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, -.42, P <.05). There was also no relationship between RXR alpha and PPARgamma 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.
Codner
E
E
V A San Diego Healthcare System, San Diego, CA 92161, USA.
Loviscach
M
M
Ciaraldi
T P
TP
Rehman
N
N
Carter
L
L
Mudaliar
S
S
Henry
R R
RR
D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000096:biosynthesis*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000819:agonists / Q000096:biosynthesis* / Q000378:metabolism
D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D005947:Glucose