Rosaglitazone (RGZ) decreases renal damage in spontaneously diabetic Goto‐Kakizaki (GK) rats

Abstract

Rosiglitazone (RGZ) is a member of a class of oral antidiabetic agents that increase insulin sensitivity and improve glucose tolerance. It was reported that in patients with type II diabetes and nephropathy RGZ also decreased blood pressure and albuminuria. We hypothesized that administration of RGZ to spontaneously type II diabetic GK rats would decrease diabetes-induced renal damage by inhibiting the inflammatory component. Twelve week old male GK rats were treated for four weeks with RGZ (n=4, 10mg/kg). RGZ treatment did not alter plasma insulin levels, but significantly decreased blood glucose levels after two weeks of treatment (150 ± 8 and 115 ± 2 mg/dL for vehicle and RGZ treated groups, P<0.05). Urinary albumin excretion, a marker of renal damage, decreased from 1.6 ± 0.4 mg/day in control animals to 0.7 ± 0.1 mg/day in the RGZ treated group (P<0.05). Monocyte chemoattractant protein-1 excretion, a marker of inflammation, was also decreased with RGZ treatment (7.8 ± 1.0 and 5.2 ± 0.5 pg/day for vehicle and RGZ treated groups, P<0.05). RGZ treatment did not alter cortical COX-1 protein levels, but decreased inducible COX-2 protein levels by 32%. This was accompanied by a 38% decrease in urinary PGE2 excretion. Together, these data support the hypothesis that RGZ treatment decreases renal damage in an animal model of type II diabetes by decreasing the inflammatory component and reducing COX-2 protein and metabolites.