Increased susceptibility of db/db mice to rosiglitazone-induced plasma volume expansion: role of dysregulation of renal water transporters

摘要: Thiazolidinediones (TZDs), which are synthetic peroxisome proliferator-activated receptor subtype-γ (PPARγ), agonists highly effective for treatment of type 2 diabetes. However, the side effect fluid retention has significantly limited their application. Most previous studies addressing TZD-induced employed healthy animals. The underlying mechanism this phenomenon is still incompletely understood, particularly in setting disease state. present study was undertaken to examine rosiglitazone (RGZ)-induced db/db mice and further investigate mechanism. In response RGZ treatment, exhibited an accelerated plasma volume expansion as assessed by hematocrit (Hct) fluorescent nanoparticles, parallel with a greater increase body weight, compared lean controls. RGZ-induced retention, urinary Na+ excretion urine were increased mice. contrast, natriuretic diuretic responses blunted decrease concentration osmolality, contrasting unchanged levels Imunoblotting analysis showed downregulation renal aquaporin (AQP) expression but not Renal AQP3 protein unaffected elevated Na+/H+ exchanger-3 (NHE3) NKCC2 either mouse strain. Together these results suggest that controls, part due inappropriate water transporters.