Research Article
Novel Partial Agonist of PPAR-Gamma for Treatment of Diabetic Neuropathy in Rats
Author(s): Lídia M Lima, Margarete M Trachez, Josenildo Segundo Chaves de Araujo, Jaqueline Soares da Silva, Daniel Nascimento do Amaral, Roberto T Sudo, Eliezer J Barreiro and Gisele Zapata-SudoLídia M Lima, Margarete M Trachez, Josenildo Segundo Chaves de Araujo, Jaqueline Soares da Silva, Daniel Nascimento do Amaral, Roberto T Sudo, Eliezer J Barreiro and Gisele Zapata-Sudo
This work describes a novel ligand for peroxisome proliferator-activated receptor gamma (PPARgamma) and its hypoglycemic and analgesic activity in a murine model of diabetes-induced neuropathic pain. The molecular recognition of LASSBio-1772 by a PPARgamma binding domain showed that the compound is a partial agonist. Four weeks after male Wistar rats received a single intravenous injection of streptozotocin (STZ, 60 mg/kg), plasma glucose levels were increased from 92.5 ± 3.7 to 465.0 ± 21.6 mg/dL (P < 0.01) and serum insulin was reduced from 66.8 ± 7.8 to 25.5 ± 5.6 pmol/L (P<0.01). Diabetic animals were then, treated with either vehicle or LASSBio-1772 (50 mg/kg, i.p.) daily for 7 days. LASSBio-1772 significantly reduced blood glucose levels to 242.0 ± 55.1 mg/dL (P<0.05) and increased insulin levels to 58.7 ± 14.8 pmol/L (P<0.05.. View More»
