A novel peroxisome proliferator-activated receptor (PPAR)gamma agonist, NIP-222, reduces urinary albumin excretion in streptozotocin-diabetic mice independent of PPARgamma activation

• Published in: Metabolism, clinical and experimental Vol. 52; no. 12; pp. 1633 - 1637
• Main Authors: Yotsumoto, Takashi, Naitoh, Takeshi, Kanaki, Tatsuro, Matsuda, Maho, Tsuruzoe, Nobutomo
• Format: Journal Article
• Language: English
• Published: United States 01.12.2003
• Subjects: Albuminuria - complications; Albuminuria - drug therapy; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Blood Glucose - metabolism; Blood Pressure - drug effects; Body Weight - drug effects; Captopril - pharmacology; Chromans - pharmacology; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - urine; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Genes, Reporter - genetics; Hypoglycemic Agents - pharmacology; Kidney - drug effects; Kidney - pathology; Luciferases - genetics; Male; Mice; Organ Size - drug effects; Plasmids - genetics; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - metabolism; Thiazolidinediones - pharmacology; Transcription Factors - agonists; Transcription Factors - metabolism; Troglitazone; Urodynamics - drug effects
• ISSN: 0026-0495

NIP-222 is a novel peroxisome proliferator-activated receptor (PPAR)gamma agonist. This study provides evidence that NIP-222 decreases urinary albumin excretion (UAE) in diabetic mice independent of its PPARgamma activation. We compared the effect of NIP-222 and another PPARgamma agonist, troglitazone, on UAE, plasma glucose level, blood pressure, and creatinine clearance (C(cr)) in streptozotocin (STZ)-induced diabetic mice. Treatment for 3 weeks with NIP-222 (30 mg/kg) was associated with a significant decrease in UAE without any change in blood pressure, creatinine clearance, or plasma glucose level. In contrast, UAE did not decrease in mice treated with troglitazone (300 mg/kg). These results indicate that NIP-222 has PPARgamma independent effects on UAE in diabetic mice and suggest that this agent may have potential to minimize the development and progression of diabetic nephropathy.