Subcutaneous adipose tissue expression of plasminogen activator inhibitor-1 (PAI-1) in nondiabetic and Type 2 diabetic subjects

Objective Increased plasma levels of plasminogen activator inhibitor-1 (PAI -1) have been suggested to be a part of the insulin resistance syndrome, an d recent data suggest that adipose tissue participates in the production of PAI-1. We examined the expression and insulin regulation of subcutaneous a dipose tissue PAI-1 mRNA and its relationship to insulin sensitivity. Design A cross-sectional study involving five lean (60.0+/-3.1 years, BMI 2 3.5+/-0.5 kg/m(2)) and six obese nondiabetic men (56.0+/-3.1 years, BMI 30. 4+/-0.7 kg/m(2)), and six obese Type 2 diabetic men (61.4+/-3.2 years, BMI 31.8+/-1.0 kg/m(2)). Measurements Subcutaneous adipose tissue PAI-1 mRNA and insulin sensitivity were quantified using RT-competitive PCR and euglycemic hyperinsulinemic c lamp technique, respectively. Results Subcutaneous adipose tissue PAI-1 mRNA levels were higher in obese nondiabetic and Type 2 diabetic men than in lean nondiabetic men. PAI-1 mRN A levels decreased in the three groups during a 240-min euglycemic hyperins ulinemic clamp (P<0.05 for all groups), and a similar reduction was observe d during a 240-min saline control study indicating that adipose tissue PAI- 1 gene expression has diurnal variation and is not acutely controlled by hy perinsulinemia. The basal PAI-1 mRNA levels correlated positively with BMI, and waist-to-hip ratio; and negatively with whole-body glucose disposal ra te in nondiabetic men. Conclusions Subcutaneous adipose tissue PAI-1 mRNA expression is increased in obese nondiabetic or in Type 2 diabetic men. Subcutaneous adipose tissue PAI-1 mRNA expression is increased in proportion to visceral obesity and t o the level of whole-body insulin resistance. Subcutaneous adipose tissue P AI-1 mRNA expression is not acutely regulated by insulin, and it is subject to a diurnal variation. Copyright (C) 2000 John Wiley & Sons, Ltd.