Hepatic over-expression of peroxisome proliferator activated receptor γ2 in the ob/ob mouse model of non-insulin dependent diabetes mellitus

Studies of the molecular basis of insulin resistance have focused on the peroxisome proliferator activated receptor gamma (PPAR gamma, gamma1 and gamma2). The aim of this study was to determine whether the insulin resistance in liver of diabetic animals is associated with abnormal expression of these receptors. PPAR gamma mRNA and protein expression levels were quantified in liver of 9-week-old male ob/ob mice as a model of diabetes and compared to age- and gender-matched wild type control animals of the same genetic background. Semi-quantitative reverse transcription-polymerase chain reaction, using 18S rRNA as an internal standard, indicated that PPAR gamma2 mRNA was significantly upregulated in ob/ob liver vs. that in wild type mice. Western blotting revealed greater immunoreactivity of PPAR gamma2 in liver from ob/ob mice relative to that in wild type mice. An index of insulin resistance (product of serum glucose and insulin concentration) was correlated with liver PPAR gamma2 mRNA expression (r = 0.776; p < 0.001). The findings that liver PPAR gamma2 expression is (1) significantly elevated in the ob/ob model of diabetes and (2) positively associated with an index of insulin resistance, suggests a possible compensatory response through which type II diabetic and obese organisms strive to maintain insulin sensitivity of the liver.